生物纳米通道用于神经退行性疾病致病蛋白和DNA的单分子研究
|
摘要
蛋白质和DNA等生物大分子是生命活动的重要化学基础,生物分子构象多种多样,且能与其它分子以不同结合状态存在。常规物质分析技术仅从宏观了解物质属性,而对单个分子及分子间的相互作用不能进行准确、有效表达。近十年发展起来的高灵敏单分子检测手段不仅能对单个分子进行观察和鉴定,而且为生物大分子的结构和功能作用研究提供直接信息,可用于研究传统分析方法及生物学方法难以解决的问题,为分子生物学、化学和医学的更深层次上的研究提供一种新的分析手段。其中,基于纳米通道检测技术建立的高效、快速单分子检测方法,越来越为分析科学家们所关注。纳米通道是以具有孔状结构的α-溶血素(α-Hemolysin)蛋白在仿生界面磷脂双层膜上形成生物纳米通道为基础,利用通道中离子流变化在单分子水平上对生物大分子的结构进行研究。许多疾病的发生均与蛋白质结构变化相关,本文以此为出发点,利用具有前庭结构的小孔径α-溶血素纳米通道探究神经退行性疾病致病纤维蛋白的空间结构和聚集状态变化,为神经退行性疾病的早期诊断和药物筛选提供了新方法。开发出具有对称结构的大孔径生物纳米通道SP1(Stable Protein),在单分子水平上分析DNA分子形态变化,为DNA链与对称型生物纳米通道内部作用研究提供新的研究模型,有望扩展现有生物纳米通道成孔材料的应用范围。具体研究内容如下：1、a-溶血素生物纳米通道用于阿兹海默症(Alzheimer Disease, AD)致病蛋白(Aβ42)结构变化研究
利用α-溶血素纳米通道单分子检测装置及控制分析系统,在电场驱动下实时观察Aβ42单体及其寡聚物在纳米通道中的结构变化信息。经分析寡聚物被纳米通道捕获时的阻断电流值约为96.58±0.20pA,阻断时间长达数秒,表明Aβ42单体自聚集形成寡聚物能够被纳米通道所捕获。加入小分子药物调控后,发现常用淀粉样蛋白染色剂刚果红可抑制Aβ42的聚集,形成结构较小的单体,单体穿过纳米通道产生的特征阻断电流值约为25.47±0.30pA。常用药物包裹剂p-环糊精能够促进Aβ42的快速聚集,形成较大体积聚集物而无法进入纳米通道。通过纳米通道可在单分子水平上观察Aβ42经小分子药物作用后结构变化,为AD的早期诊断及药物筛选提供了新方法。2、α-溶血素生物纳米通道对帕金森症(Parkinson Disease, PD)致病蛋白聚集行为研究
通过α-溶血素纳米通道在单分子水平上对PD致病蛋白α-synuclein纤维化行为进行研究。野生型和突变型α-synuclein均为研究对象,在体外生理环境下,α-synuclein单体C端带有负电且为伸展状态,在电场驱动下能够以线性从纳米通道负极端运动至正极端。外加电压大于100mV时,较强电场作用可改变α-synuclein单体分子内静电作用,使其形成部分折叠的中间态被α-溶血素前庭捕获,使阻断电流降低至约20.0±1.0pA,该中间体进一步折叠使阻塞电流降低至约5.0±0.5pA。而不断降低电压可使分子间静电作用减弱,折叠趋势逐渐减小,当电压小于40mV时,折叠分子可退出通道入口处,由此,我们通过纳米通道检测手段在单分子水平上证明α-syn纤维化的初始阶段存在部分折叠的结构变化中间体。同一体系中,引入还原型海藻糖分子,证明其对突变型蛋白(A53T α-synuclein)聚集具有抑制作用而对野生型蛋白聚集无抑制作用,由此推断海藻糖对突变型α-synuclein的抑聚集是通过改变β-叠片表面水层张力而破坏分子间氢键作用,这对临床上PD的早期治疗和早预防具有一定启示意义。
3、基于稳定蛋白(Stable Protein One, SP1)纳米通道对DNA结构分析
SP1蛋白经简易操作即可在磷脂双层膜上形成内径约为3nm的纳米通道,通道电导约为1.5nS。将其应用于区分不同结构和链长的单链DNA,证明含有同样碱基的单链DNA分子,刚性链状结构分了穿过通道时间与链长成正比,结构较为松散的非链状结构分子则不遵守此规则。同等实验条件下,相同单链DNA通过α-溶血素纳米通道的速率约为SP1纳米通道的2-4倍,表明SP1纳米通道以其较短的通道长度和没有前庭的圆柱体状结构在核酸序列检测中能够减缓DNA链穿过的速率,有望成为用于新一代基因测序的天然成孔材料,并用于其他生物大分子单分子水平检测,极大地扩宽了现有生物纳米成孔材料的应用范围。
The biopolymers including protein and DNAs are important for present-day life. The biopolymers own various conformations and interact with differnet molecules. Routine analytical methods just study the overall properity of materials rather than the interaction between different moleucles at single molecule level. Sensitive single-molecule detection (SMD) technique not ony qualitative observe single biopolymer but also provide structural information of every biopolymer. SMD could offer a novel analytical technique in deeper studying biopolymers with the problems that are hardly solved by traditional methods. Nanopore, as a efficient and radip single molecule detection method, has drawn scientist attation. α-hemolysin (α-HL) self-assembled on lipid bilayer to form a nano-scale pore, which could resistant high applid potential and ionic strength. The blockade events produced by translocation through α-HL are related to the conformational change, which remind us to detect pathogenesis-related proteins by using α-HL nanopore. From this point, we utilized thea-HL nanopore which contains a vestibule to explore the conformation change of the amyloid protein related to neurodegenerative diseases. By observing the aggregating change of amyloid protein at single-molecule level, we offered a novel method for the early diagnosis and drug screen for neurodegenerative disease. Furthermore, we developed a new biological nanopore based on SP1protein to observe the structural changes of single DNA inside the pore. Using SP1nanopore to investigate single molecules detection broaden the existing research areas from unsymmetrical biological nanopore to symmetrical biological nanopore, as well as establishing the theoretical model of the interaction between DNA and SP1nanopore. The detail research contents are as follows:
1. Nanopore analysis of β-amyloid peptide aggregation transition induced by small molecules
β-Amyloid42(Aβ42) is the predominant form of the amyloid peptide, which is found in the plaques of the brains of Alzheimer's (AD) patients and is one of the most abundant components in amyloid aggregates. Information of the Aβ42aggregation states is essential for developing an understanding of the pathologic process of amyloidoses. Here, we used α-hemolysin (α-HL) pores to probe the different aggregation transition of Aβ42in the presence of β-cyclodextrin (β-CD), a promoter of Aβ42aggregations, and in the presence of Congo red (CR), an inhibitor of aggregations. Analyzing the characteristic transit duration times and blockade currents showed that β-CD and CR have opposite effects on the aggregation of Aβ42. Translocation events of the monomeric Aβ42peptide (i=25.47pA) were significantly lower in amplitude currents than protofilaments (i=96.25pA), and protofilaments were captured in the α-HL nanopore with a longer duration time. CR binds to Aβ42and its peptide fibrils by reducing the aggregated fibrils formation. In this process it is assumed CR interferes with intermolecular hydrogen bonding present in the aggregates. In contrast to CR, β-CD promotes the aggregation of Aβ42. These differences can readily be analyzed by monitoring the corresponding characteristic blockade events using a biological α-HL nanopore.
2. Analysis of α-synuclein fibrillation using α-HL nanopore
The fibrils procedure of α-synuclein is investigated in physiological condition by α-HL nanopore. The natively unfolded α-synuclein monomer will translocate through α-HL nanopore by applied potential. Changing the poteinal, a partially folded intermediate are involved in the critical early stage of the structural transformation which is monitored by captured inside the vestibule of α-HL nanopore with the capture current of20±1pA. Further blocking of the intermediate will produce block current of5±0.5pA, which revealed that the early-stage fibril of α-syn is affected by intramolecular electrostatic interaction. In addition, trehalose inhibited the fibriation by changing the surface hydrophobic interaction of A53T α-synuclein without any inhibition of WT α-synuclein. The result also proved that the interpeptide hydrophobic interactions in the elongation of A53T α-synuclein protofilaments cannot be greatly weakened by trehalose. The inhibitory effect of trehalose is partially nucleation specific, whereby formation of protofibril or nuclei is prevented. This work provides unique insights into the earliest steps of α-synuclein aggregation pathway and should provide the basis for the development of drugs that can prevent aggregation at the initial stage.
3. Single-molecule DNA detection using novel SP1protein nanopore
Nanopore plays a central role in single-molecule analysis since the ionic current blockades they produce provide information about the identity, conformation and dynamic of target molecules. The SP1protein has remarkable stability under extreme environmental conditions and it exhibits a wider symmetrical channel constriction that is promising for DNA detection. Here, SP1protein as a new type of nanopore is primarily described and the functions of SP1nanopore were utilized to distinguish single-strand DNA at single-molecule level. It is found that the predominant effect on the blockage interaction originates from the quasi-rigid structures of the biopolymers. These are almost unaffected by the lengths of the polymer chains mainly in threading through the symmetrical SP1nanopore linearly. By comparing with α-HL nanopore, it is speculated that the geometry of SP1could slow down the translocating velocity of ssDNA. Thus, the SP1pore material has potential advantages may be used for future DNA sequencing applications. Non-vestibule structure results in ssDNAs entering the SP1nanopores without any vector constriction or direction followed by passing randomly. Using SP1nanopore to investigate single molecules detection broaden the existing research areas from unsymmetrical biological nanopore to symmetrical biological nanopore.
利用α-溶血素纳米通道单分子检测装置及控制分析系统,在电场驱动下实时观察Aβ42单体及其寡聚物在纳米通道中的结构变化信息。经分析寡聚物被纳米通道捕获时的阻断电流值约为96.58±0.20pA,阻断时间长达数秒,表明Aβ42单体自聚集形成寡聚物能够被纳米通道所捕获。加入小分子药物调控后,发现常用淀粉样蛋白染色剂刚果红可抑制Aβ42的聚集,形成结构较小的单体,单体穿过纳米通道产生的特征阻断电流值约为25.47±0.30pA。常用药物包裹剂p-环糊精能够促进Aβ42的快速聚集,形成较大体积聚集物而无法进入纳米通道。通过纳米通道可在单分子水平上观察Aβ42经小分子药物作用后结构变化,为AD的早期诊断及药物筛选提供了新方法。2、α-溶血素生物纳米通道对帕金森症(Parkinson Disease, PD)致病蛋白聚集行为研究
通过α-溶血素纳米通道在单分子水平上对PD致病蛋白α-synuclein纤维化行为进行研究。野生型和突变型α-synuclein均为研究对象,在体外生理环境下,α-synuclein单体C端带有负电且为伸展状态,在电场驱动下能够以线性从纳米通道负极端运动至正极端。外加电压大于100mV时,较强电场作用可改变α-synuclein单体分子内静电作用,使其形成部分折叠的中间态被α-溶血素前庭捕获,使阻断电流降低至约20.0±1.0pA,该中间体进一步折叠使阻塞电流降低至约5.0±0.5pA。而不断降低电压可使分子间静电作用减弱,折叠趋势逐渐减小,当电压小于40mV时,折叠分子可退出通道入口处,由此,我们通过纳米通道检测手段在单分子水平上证明α-syn纤维化的初始阶段存在部分折叠的结构变化中间体。同一体系中,引入还原型海藻糖分子,证明其对突变型蛋白(A53T α-synuclein)聚集具有抑制作用而对野生型蛋白聚集无抑制作用,由此推断海藻糖对突变型α-synuclein的抑聚集是通过改变β-叠片表面水层张力而破坏分子间氢键作用,这对临床上PD的早期治疗和早预防具有一定启示意义。
3、基于稳定蛋白(Stable Protein One, SP1)纳米通道对DNA结构分析
SP1蛋白经简易操作即可在磷脂双层膜上形成内径约为3nm的纳米通道,通道电导约为1.5nS。将其应用于区分不同结构和链长的单链DNA,证明含有同样碱基的单链DNA分子,刚性链状结构分了穿过通道时间与链长成正比,结构较为松散的非链状结构分子则不遵守此规则。同等实验条件下,相同单链DNA通过α-溶血素纳米通道的速率约为SP1纳米通道的2-4倍,表明SP1纳米通道以其较短的通道长度和没有前庭的圆柱体状结构在核酸序列检测中能够减缓DNA链穿过的速率,有望成为用于新一代基因测序的天然成孔材料,并用于其他生物大分子单分子水平检测,极大地扩宽了现有生物纳米成孔材料的应用范围。
The biopolymers including protein and DNAs are important for present-day life. The biopolymers own various conformations and interact with differnet molecules. Routine analytical methods just study the overall properity of materials rather than the interaction between different moleucles at single molecule level. Sensitive single-molecule detection (SMD) technique not ony qualitative observe single biopolymer but also provide structural information of every biopolymer. SMD could offer a novel analytical technique in deeper studying biopolymers with the problems that are hardly solved by traditional methods. Nanopore, as a efficient and radip single molecule detection method, has drawn scientist attation. α-hemolysin (α-HL) self-assembled on lipid bilayer to form a nano-scale pore, which could resistant high applid potential and ionic strength. The blockade events produced by translocation through α-HL are related to the conformational change, which remind us to detect pathogenesis-related proteins by using α-HL nanopore. From this point, we utilized thea-HL nanopore which contains a vestibule to explore the conformation change of the amyloid protein related to neurodegenerative diseases. By observing the aggregating change of amyloid protein at single-molecule level, we offered a novel method for the early diagnosis and drug screen for neurodegenerative disease. Furthermore, we developed a new biological nanopore based on SP1protein to observe the structural changes of single DNA inside the pore. Using SP1nanopore to investigate single molecules detection broaden the existing research areas from unsymmetrical biological nanopore to symmetrical biological nanopore, as well as establishing the theoretical model of the interaction between DNA and SP1nanopore. The detail research contents are as follows:
1. Nanopore analysis of β-amyloid peptide aggregation transition induced by small molecules
β-Amyloid42(Aβ42) is the predominant form of the amyloid peptide, which is found in the plaques of the brains of Alzheimer's (AD) patients and is one of the most abundant components in amyloid aggregates. Information of the Aβ42aggregation states is essential for developing an understanding of the pathologic process of amyloidoses. Here, we used α-hemolysin (α-HL) pores to probe the different aggregation transition of Aβ42in the presence of β-cyclodextrin (β-CD), a promoter of Aβ42aggregations, and in the presence of Congo red (CR), an inhibitor of aggregations. Analyzing the characteristic transit duration times and blockade currents showed that β-CD and CR have opposite effects on the aggregation of Aβ42. Translocation events of the monomeric Aβ42peptide (i=25.47pA) were significantly lower in amplitude currents than protofilaments (i=96.25pA), and protofilaments were captured in the α-HL nanopore with a longer duration time. CR binds to Aβ42and its peptide fibrils by reducing the aggregated fibrils formation. In this process it is assumed CR interferes with intermolecular hydrogen bonding present in the aggregates. In contrast to CR, β-CD promotes the aggregation of Aβ42. These differences can readily be analyzed by monitoring the corresponding characteristic blockade events using a biological α-HL nanopore.
2. Analysis of α-synuclein fibrillation using α-HL nanopore
The fibrils procedure of α-synuclein is investigated in physiological condition by α-HL nanopore. The natively unfolded α-synuclein monomer will translocate through α-HL nanopore by applied potential. Changing the poteinal, a partially folded intermediate are involved in the critical early stage of the structural transformation which is monitored by captured inside the vestibule of α-HL nanopore with the capture current of20±1pA. Further blocking of the intermediate will produce block current of5±0.5pA, which revealed that the early-stage fibril of α-syn is affected by intramolecular electrostatic interaction. In addition, trehalose inhibited the fibriation by changing the surface hydrophobic interaction of A53T α-synuclein without any inhibition of WT α-synuclein. The result also proved that the interpeptide hydrophobic interactions in the elongation of A53T α-synuclein protofilaments cannot be greatly weakened by trehalose. The inhibitory effect of trehalose is partially nucleation specific, whereby formation of protofibril or nuclei is prevented. This work provides unique insights into the earliest steps of α-synuclein aggregation pathway and should provide the basis for the development of drugs that can prevent aggregation at the initial stage.
3. Single-molecule DNA detection using novel SP1protein nanopore
Nanopore plays a central role in single-molecule analysis since the ionic current blockades they produce provide information about the identity, conformation and dynamic of target molecules. The SP1protein has remarkable stability under extreme environmental conditions and it exhibits a wider symmetrical channel constriction that is promising for DNA detection. Here, SP1protein as a new type of nanopore is primarily described and the functions of SP1nanopore were utilized to distinguish single-strand DNA at single-molecule level. It is found that the predominant effect on the blockage interaction originates from the quasi-rigid structures of the biopolymers. These are almost unaffected by the lengths of the polymer chains mainly in threading through the symmetrical SP1nanopore linearly. By comparing with α-HL nanopore, it is speculated that the geometry of SP1could slow down the translocating velocity of ssDNA. Thus, the SP1pore material has potential advantages may be used for future DNA sequencing applications. Non-vestibule structure results in ssDNAs entering the SP1nanopores without any vector constriction or direction followed by passing randomly. Using SP1nanopore to investigate single molecules detection broaden the existing research areas from unsymmetrical biological nanopore to symmetrical biological nanopore.
引文
[1]Betz, W.; Sakmann. B., Effects of proteolytic enzymes on function and structure of frog neuromuscular junctions. The Journal of physiology.1973,230(3):p.673.
[2]Neher, E.; Sakmann, B.; Steinbach, J. H., The extracellular patch clamp:a method for resolving currents through individual open channels in biological membranes. Pflugers Archiv.1978,375(2):p.219-228.
[3]Hamill, O.; Marty, A.; Neher, E.; Sakmann, B.; Sigworth, F., Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Archiv 1981,391 (2),85-100.
[4]http://www.nobelprize.org/nobel_prizes/medicine/laureates/1991/sakmann-autobio.html
[5]Bull, B.; Schneiderman, M.; Brecher, G., Platelet counts with the coulter counter. American Journal of Clinical Pathology.1965,44(6):678.
[6]McNally, B., Next generation nanopore-based DNA sequencing.2012, Boston University.
[7]Schadt, E.E.; Turner, S.; Kasarskis, A., A window into third-generation sequencing. Human Molecular Genetics.2010,19(R2):R227-R240.
[8]Branton, D.; Deamer, D. W.; Marziali, A.; Bayley, H.; Benner, S. A.; Butler, T.; Di Ventra, M.; Garaj, S.; Hibbs, A.; Huang, X. H.; Jovanovich, S. B.; Krstic, P. S.; Lindsay, S.; Ling, X. S. S.; Mastrangelo, C. H.; Meller, A.; Oliver, J. S.; Pershin, Y. V.; Ramsey, J. M.; Riehn, R.; Soni, G. V.; Tabard-Cossa, V.; Wanunu, M.; Wiggin, M.; Schloss, J. A., The potential and challenges of nanopore sequencing. Nature Biotechnology.2008,26(10):1146-1153.
[9]Gu, L.; Cheley, S.; Bayley, H., Capture of a single molecule in a nanocavity. Science. 2001,291(5504):636.
[10]Kang, X. F.; Cheley, S.; Rice-Ficht, A. C.; Bayley, H., A storable encapsulated bilayer chip containing a single protein nanopore. Journal of the American Chemical Society.2007, 129(15):4701-4705.
[11]White, R.; Ervin, E.; Yang, T.; Chen, X.; Daniel, S.; Cremer, P.; White, H., Single ion-channel recordings using glass nanopore membranes. Journal of the American Chemical Society,2007.129(38):11766-11775.
[12]Shim, J.; Gu, L., Stochastic sensing on a modular chip containing a single-ion channel.Analtical Chemistry.2007,79(6):2207-2213.
[13]Zhang, B.; Galusha, J.; Shiozawa, P.; Wang, G.; Bergren, A.; Jones, R.; White, R.; Ervin, E.; Cauley, C.; White, H., Bench-top method for fabricating glass-sealed nanodisk electrodes, glass nanopore electrodes, and glass nanopore membranes of controlled size. Analytical Chemistry.2007,79(13):4778-4787.
[14]Kasianowicz, J.J.; Bezrukov, S. M., Protonation dynamics of the a-toxin ion channel from spectral analysis of pH-dependent current fluctuations. Biophysical Journal.1995,69(1): 94-105.
[15]Movileanu, L.; Cheley, S.; Howorka, S.; Braha, O.; Bayley, H., Location of a constriction in the lumen of a transmembrane pore by targeted covalent attachment of polymer molecules. Journal of General Physiology.2001,117(3):239-251.
[16]Braha, O.; Gu, L. Q.; Zhou, L.; Lu, X.; Cheley, S.; Bayley, H., Simultaneous stochastic sensing of divalent metal ions. Nature Biotechnology.2000,18(9):1005-1007.
[17]Guan, X.; Gu, I... Q.; Cheley, S.; Braha, O.; Bayley, H., Stochastic sensing of TNT with a genetically engineered pore. Chembiochem.2005,6(10):1875-1881.
[18]Howorka, S.; Movileanu, L.; Braha, O.; Bayley, H., Kinetics of duplex formation for individual DNA strands within a single protein nanopore. Proceedings of the National Academy of Sciences of the United States of America.2001,98(23):12996-13001.
[19]Howorka, S.; Cheley, S.; Bayley, H., Sequence-specific detection of individual DNA strands using engineered nanopores. Nature Biotechnology.2001,19(7):636-639.
[20]Howorka, S.; Movileanu, L.; Lu, X.; Magnon, M.; Cheley, S.; Braha, O.; Bayley, H., A protein pore with a single polymer chain tethered within the lumen. Journal of the American Chemical Society.2000,122(11):2411-2416.
[21]Gu, L.-Q.; Bayley,H., Interaction of the Noncovalent Molecular Adapter, β-Cyclodextrin, with the Staphylococcal a-Hemolysin Pore. Biophysical Journal.2000,79(4):1967-1975.
[22]Stoddart, D.; Heron, A. J.; Mikhailova, E.; Maglia, G.; Bayley, H., Single-nucleotide discrimination in immobilized DNA oligonucleotides with a biological nanopore. Proceedings of the National Academy of Sciences of the United States of America.2009,106(19): 7702-7707.
[23]Clarke, J.; Wu, H. C.; Jayasinghe, L.; Patel, A.; Reid, S.; Bayley, H., Continuous base identification for single-molecule nanopore DNA sequencing. Nature nanotechnology.2009, 4(4):265-270.
[24]Cherf, G. M.; Lieberman, K. R.; Rashid, H.; Lam, C. E.; Karplus, K.; Akeson, M., Automated forward and reverse ratcheting of DNA in a nanopore at 5-A precision. Nature Biotechnology.2012,30(4):344-348.
[25]Lieberman, K. R.; Cherf, G. M.; Doody, M. J.; Olasagasti, F.; Kolodji, Y.; Akeson, M., Processive replication of single DNA molecules in a nanopore catalyzed by phi29 DNA polymerase. Journal of the American Chemical Society.2010,132(50):17961-17972.
[26]Faller, M., The Structure of a Mycobacterial Outer-Membrane Channel. Science.2004, 303(5661):1189-1192.
[27]Butler, T.; Pavlenok, M.; Derrington, I.; Niederweis, M.; Gundlach, J., Single-molecule DNA detection with an engineered MspA protein nanopore. Proceedings of the National Academy of Sciences.2008,105(52):20647-20652.
[28]Derrington, I. M.; Butler, T. Z.; Collins, M. D.; Manrao, E.; Pavlenok, M.; Niederweis, M.; Gundlach, J. H., Nanopore DNA sequencing with MspA. Proceedings of the National Academy of Sciences.2010,107(37):16060-16065.
[29]Manrao, E. A.; Derrington, I. M.; Laszlo, A. H.; Langford, K. W.; Hopper, M. K.; Gillgren, N.; Pavlenok, M.; Niederweis, M.; Gundlach, J. H., Reading DNA at single-nucleotide resolution with a mutant MspA nanopore and phi29 DNA polymerase. Nature Biotechnology.2012,30(4):349-353.
[30]Wendell, D.; Jing, P.; Geng, J.; Subramaniam, V.; Lee, T. J.; Montemagno, C.; Guo, P., Translocation of double-stranded DNA through membrane-adapted phi29 motor protein nanopores. Nature nanotechnology.2009,4(11):765-772.
[31]Movileanu, L.; Bayley, H., Peptide binding to a transmembrane protein pore. Biophysical Journal.2005,88(1):552A-552A.
[32]Movileanu, L.; Howorka, S.; Braha, O.; Bayley, H., Detecting protein analytes that modulate transmembrane movement of a polymer chain within a single protein pore. Nature Biotechnology.2000,18(10):1091-1095.
[33]Movileanu, L., Interrogating single proteins through nanopores:challenges and opportunities. Trends in Biotechnology.2009,27(6):333-341.
[34]Movileanu, L.; Schmittschmitt, J. P.; Scholtz, J. M.; Bayley, H., Interactions of peptides with a protein pore. Biophysical Journal.2005,89(2):1030-1045.
[35]Okuyama, K.; Hongo, C.; Fukushima, R.; Wu, G.; Narita, H.; Noguchi, K.; Tanaka, Y.; Nishino, N., Crystal structures of collagen model peptides with Pro-Hyp-Gly repeating sequence at 1.26 resolution:Implications for proline ring puckering. Peptide Science.2004, 76(5):367-377.
[36]Sutherland, T. C.; Long, Y. T.; Stefureac, R. I.; Bediako-Amoa, I.; Kraatz, H. B.; Lee, J. S., Structure of peptides investigated by nanopore analysis. Nano Letters.2004,4(7): 1273-1277.
[37]Long, Y.; Zhang, M., Self-assembling bacterial pores as components of nanobiosensors for the detection of single peptide molecules. Science in China Series B:Chemistry.2009, 52(6):731-733.
[38]Stefureac, R.; Long, Y.-T.; Kraatz, H.-B.; Howard, P.; Lee, J. S., Transport of a-Helical peptides through α-Hemolysin and aerolysin pores. Biochemistry.2006,45(30):9172-9179.
[39]Wolfe, A. J.; Mohammad; Cheley, S.; Bayley, H.; Movileanu, L., Catalyzing the Translocation of polypeptides through attractive interactions. Journal of the American Chemical Society.2007,129(45):14034-14041.
[40]Stefureac, R. I.; Lee, J. S., Nanopore analysis of the folding of zinc fingers. Small.2008, 4(10):1646-1650.
[41]Oukhaled, G.; Mathe, J.; Biance, A. L.; Bacri, L.; Betton, J. M.; Lairez, D.; Pelta, J.; Auvray, L., Unfolding of proteins and long transient conformations detected by single nanopore recording. Physical Review Letters.2007,98:15801.
[42]Stefureac, R.; Waldner, L.; Howard, P.; Lee, J. S., Nanopore analysis of a small 86-residue protein. Small.2008,4(1):59-63.
[43]Akeson, M.; Branton, D.; Kasianowicz, J.; Brandin, E.; Deamer, D., Microsecond time-scale discrimination among polycytidylic acid, polyadenylic acid, and polyuridylic acid as homopolymers or as segments within single RNA molecules. Biophysical Journal.1999, 77(6):3227-3233.
[44]David R.-L.; Bayley, H., Multistep protein unfolding during nanopore translocation. Nature nanotechnology.2013,8:288-295.
[45]Nivala, J.; Marks, D. B.; Akeson, M., Unfoldase-mediated protein translocation through an α-hemolysin nanopore. Nature Biotechnology.2013,31 (3),247-250.
[46]Song, L.; Hobaugh, M.; Shustak, C.; Cheley, S.; Bayley, U.; Gouaux, J., Structure of staphylococcal α-hemolysin, a heptameric transmembrane pore. Science.1996,274(5294): 1859-1866.
[47]Mohammad, M. M.; Prakash, S.; Matouschek, A.; Movileanu, L., Controlling a single protein in a nanopore through electrostatic traps. Journal of the American Chemical Society. 2008,130(12):4081-4088.
[48]Cockroft, S. L.; Chu, J.; Amorin, M.; Bayley, H.; Ghadiri, M. R., A single-molecule nanopore device detects DNA polymerase activity with single-nucleotide resolution. Journal of the American Chemical Society.2008,130(3):818-820.
[49]Cheley, S.; Xie, H. Z.; Bayley, H., A genetically encoded pore for the stochastic detection of a protein kinase. Chembiochem.2006,7(12):1923-1927.
[50]Bretscher, M.S., Asymmetrical lipid bilayer structure for biological membranes. Nature. 1972,236(61):11-12.
[51]Deamer, D., Nanopore analysis of nucleic acids bound to exonucleases and polymerases. Annual review of biophysics.2010,39:79-90.
[52]Kasianowicz, J. J.; Henrickson, S. E.; Weetall, H. H.; Robertson, B., Simultaneous multianalyte detection with a nanometer-scale pore. Analytical Chemistry.2001,73(10): 2268-2272.
[53]Hornblower, B.; Coombs, A.; Whitaker, R.; Kolomeisky, A.; Picone, S.; Meller, A.; Akeson, M., Single-molecule analysis of DNA-protein complexes using nanopores. Nature Methods.2007,4(4):315-318.
[54]Astier, Y.; Kainov, D. E.; Bayley, H.; Tuma, R.; Howorka, S., Stochastic detection of motor protein-RNA complexes by single-channel current recording. Chemphyschem.2007, 8(15):2189-2194.
[55]Adler, A.; Grossman, L.; Fasman, G., Single-stranded oligomers and polymers of cytidylic and 2'-deoxycytidylic acids:Comparative optical rotatory studies. Proceedings of the National Academy of Sciences of the United States of America.1967,57(2):23.
[56]Hurt, N.; Wang, H.; Akeson, M.; Lieberman, K., Specific Nucleotide binding and rebinding to individual DNA polymerase complexes captured on a nanopore. Journal of the American Chemical Society.2009,131(10):3772-3778.
[57]Benner, S.; Chen, R.; Wilson, N.; Abu-Shumays, R.; Hurt, N.; Lieberman, K.; Deamer, D.; Dunbar, W.; Akeson, M., Sequence-specific detection of individual DNA polymerase complexes in real time using a nanopore. Nature nanotechnology.2007,2(11):718.
[58]Wilson, N.; Abu-Shumays, R.; Gyarfas, B.; Wang, H.; Lieberman, K.; Akeson, M.; Dunbar, W., Electronic control of DNA polymerase binding and unbinding to single DNA molecules. Journal of the American Chemical Society.2009,131(10):3772-3778.
[59]Panwar, A.S.; Muthukumar, M., Enzyme-modulated DNA translocation through a nanopore. Journal of the American Chemical Society.2009,131(51):18563-18570.
[60]Cockroft, S.L.; Chu, J.; Amorin, M; Bayley, H.; Ghadiri, M. R., A single-molecule nanopore device detects DNA polymerase activity with single-nucleotide resolution. Journal of the American Chemical Society.2008,130(3):818-820.
[61]Prusiner, S.B.; Molecular biology of prion diseases. Science.1991,252(5012): 1515-1522.
[62]Masters, C. L.; Simms, G.; Weinman, N. A.; Multhaup, G.; McDonald, B. L.; Beyreuther, K., Amyloid plaque core protein in Alzheimer disease and down syndrome. Proceedings of the National Academy of Sciences of the United States of America.1985,82(12):4245-4249.
[63]Parkinson, J., An essay on the shaking palsy.1817:Printed by Whittingham and Rowland for Sherwood, Neely, and Jones. [64] Polymeropoulos, M. H.; Higgins, J. J.; Golbe, L. I.; Johnson, W. G.; Ide, S. E.; Di Iorio, G.; Sanges, G.; Stenroos, E. S.; Pho, L. T.; Schaffer, A. A., Mapping of a gene for Parkinson's disease to chromosome 4q21-q23. Science (New York, NY),1996.274(5290):1197.
[65]Mathe, J.; Visram, H.; Viasnoff, V.; Rabin, Y.; Meller, A., Nanopore unzipping of individual DNA hairpin molecules. Biophysical Journal.2004,87(5):3205-3212.
[66]Ma, L.; Cockroft, S. L., Biological nanopores for single-molecule biophysics. Chembiochem.2010,11(1):25-34.
[67]Howorka, S.; Siwy, Z., Nanopore analytics:sensing of single molecules. Chemical Society Reviews.2009,38(8):2360-2384.
[68]Comer, J.; Aksimentiev, A., Predicting the DNA sequence dependence of nanopore ion current using atomic-resolution brownian dynamics. The Journal of Physical Chemistry C. 2012,116,3376-3393.
[69]Kawano, R.; Schibel, A. E. P.; Cauley, C.; White, H. S., Controlling the translocation of single-stranded DNA through a-hemolysin ion channels using viscosity. Langmuir.2008, 25(2):1233-1237.
[70]Ayub, M; Bayley, H., Single molecule RNA base identification with a biological nanopore. Biophysical Journal.2012,102(3):429a.
[71]Butler, T. Z.; Gundlach, J. H.; Troll, M., Ionic current blockades from DNA and RNA molecules in the a-hemolysin nanopore. Biophysical Journal.2007,93(9):3229-3240.
[72]Deamer, D.; Branton, D., Characterization of nucleic acids by nanopore analysis. Account Chemistry Research.2002,35(10):817-825.
[73]Andreeva-Kovalevskaya, Z.; Solonin, A.; Sineva, E.; Ternovsky, V., Pore-forming proteins and adaptation of living organisms to environmental conditions. Biochemistry (Moscow).2008,73(13):1473-1492.
[74]Muthukumar, M., Polymer translocation through a hole. The Journal of chemical physics. 1999,111:10371.
[75]Muthukumar, M., Translocation of a confined polymer through a hole. Physical Review Letters.2001,86(14):3188-3191.
[76]Tropini, C; Marziali, A., Multi-nanopore force spectroscopy for DNA analysis. Biophysical Journal.2007,92(5):1632-1637.
[77]Hung, W.; Chen, F.; Huang, H. W., Order-disorder transition in bilayers of diphytanoyl phosphatidylcholine. Biochimica et Biophysica Acta (BBA)-Biomembranes.2000,1467(1): 198-206.
[78]Lindsey, H.; Petersen, N.; Chan, S. I., Physicochemical characterization of 1, 2-diphytanoyl-sn-glycero-3-phosphocholine in model membrane systems. Biochimica et Biophysica Acta (BBA)-Biomembranes.1979,555(1):147-167.
[79]Boheim, G; Hanke, W.; Eibl, H., Lipid phase transition in planar bilayer membrane and its effect on carrier-and pore-mediated ion transport. Proceedings of the National Academy of Sciences of the United States of America.1980,77(6):3403-3407.
[80]Morera, F. J.; Vargas, G.; Gonzalez, C.; Rosenmann, E.; Latorre, R., Ion-channel reconstitution, In Methods in Membrane Lipids.2007, Springer.571-585.
[81]Phillips, R.; Ursell, T.; Wiggins, P.; Sens, P., Emerging roles for lipids in shaping membrane-protein function. Nature.2009,459(7245):379-385.
[82]Miller, C., Ion channel reconstitution.1986, Springer.
[83]Niles, W.; Levis, R.; Cohen, F., Planar bilayer membranes made from phospholipid monolayers form by a thinning process. Biophysical Journal.1988,53(3):327-335.
[84]White, S.; Petersen, D.; Simon, S.; Yafuso, M., Formation of planar bilayer membranes from lipid monolayers. A critique. Biophysical Journal.1976,16(5):481-489.
[85]Montal, M.; Mueller, P., Formation of bimolecular membranes from lipid monolayers and a study of their electrical properties. Proceedings of the National Academy of Sciences of the United States of America.1972,69(12):3561-3566.
[86]Peterman, M. C.; Ziebarth, J. M.; Braha, O.; Bayley, H.; Fishman, H. A.; Bloom, D., Ion channels and lipid bilayer membranes under high potentials using microfabricated apertures. Biomedical Microdevices.2002,4(3):231-236.
[87]Kang, X.; Gu, L.; Cheley, S.; Bayley, H., Single protein pores containing molecular adapters at high temperatures. Angewandte Chemie International Edition.2005,44(10): 1495-1499.
[88]Wonderlin, W.; Finkel, A.; French, R., Optimizing planar lipid bilayer single-channel recordings for high resolution with rapid voltage steps. Biophysical Journal.1990,58(2): 289-297.
[89]Mayer, M.; Kriebel, J. K.; Tosteson, M. T.; Whitesides, G. M., Microfabricated teflon membranes for low-noise recordings of ion channels in planar lipid bilayers. Biophysical Journal.2003,85(4):2684-2695.
[90]Purves, R., Microelectrode methods for intracellular recording and ionophoresis.1981, 208.:Academic Press London, UK.
[91]Hamill, O.; Marty, A.; Neher, E.; Sakmann, B.; Sigworth, F., Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Archiv.1981,391(2):85-100.
[92]Smeets, R. M. M.; Keyser, U. F.; Dekker, N.F.; Dekker, C., Noise in solid-state nanopores. Proceedings of the National Academy of Sciences of the United States of America. 2008,105(2):417.
[93]Hughes, A. J.; Daniel, S. E.; Kilford, L.; Lees, A. J., Accuracy of clinical diagnosis of idiopathic Parkinson's disease:a clinico-pathological study of 100 cases. Journal of Neurology, Neurosurgery & Psychiatry.1992,55(3):181-184.
[94]Corder, E.; Saunders, A.; Strittmatter, W.; Schmechel, D.; Gaskell, P.; Small, G.; Roses, A.; Haines, J.; Pericak-Vance, M. A., Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science.1993,261(5123):921-923.
[95]Lue, L.-F.; Brachova, L.; Civin, H. W.; Rogers, J., Inflammation, A P-amyloid Deposition, and Neurofibrillary Tangle Formation as Correlates of Alzheimer's Disease Neurodegeneration. Journal of Neuropathology & Experimental Neurology.1996,55(10): 1083-1088.
[96]Benilova, I.; Karran, E.; Strooper, B. D., The toxic Aβ oligomer and Alzheimer's disease: an emperor in need of clothes. Nature Neuroscience.2012,15(3):349-357.
[97]de la Torre, J.C., Is Alzheimer's disease a neurodegenerative or a vascular disorder? Data, dogma, and dialectics. The Lancet Neurology.2004,3(3):184-190.
[98]Ross, C.A.; Poirier, M.A., Protein aggregation and neurodegenerative disease.2004.
[99]Tanzi, R. E.; St George-Hyslop, P. H.; Haines, J. L.; Polinsky, R. J.; Nee, L.; Foncin, J.-F.; Neve, R. L.; McClatchey, A. I.; Conneally, P. M.; Gusella, J. F., The genetic defect in familial Alzheimer's disease is not tightly linked to the amyloid p-protein gene. Nature.1987,329,156-157.
[100]Mullan, M.; Crawford, F.; Axelman, K.; Houlden, H.; Lilius, L.; Winblad, B.; Lannfelt, L., A pathogenic mutation for probable Alzheimer's disease in the APP gene at the N-terminus of β-amyloid. Nature genetics.1992,1(5):345-347.
[101]Kang, J.; Lemaire, H.-G.; Unterbeck, A.; Salbaum, J. M.; Masters, C. L.; Grzeschik, K.-H.; Multhaup, G.; Beyreuther, K.; Muller-Hill, B., The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. Nature.1987,325,733-736.
[102]Dries, D.R.; Yu, G.; Herz, J., Extracting β-amyloid from Alzheimer's disease. Proceedings of the National Academy of Sciences.2012,109(9):3199-3200.
[103]Datki, Z.; Papp, R.; Zadori, D.; Soos, K.; Fulop, L.; Juhasz, A.; Laskay, G.; Hetenyi, C.; Mihalik, E.; Zarandi, M.; Penke, B., In vitro model of neurotoxicity of A beta 1-42 and neuroprotection by a pentapeptide:irreversible events during the first hour. Neurobiology of Disease.2004,17(3):507-515.
[104]Seilheimer, B.; Bohrmann, B.; Bondolfi, L.; Muller, F.; Stuber, D.; Dobeli, H., The toxicity of the Alzheimer's [beta]-amyloid peptide correlates with a distinct fiber morphology. Journal of Structural Biology.1997,119(1):59-71.
[105]Xu, Y.; Shen, J.; Luo, X.; Zhu, W.; Chen, K.; Ma, J.; Jiang, H., Conformational transition of amyloid β-peptide. Proceedings of the National Academy of Sciences of the United States of America.2005,102(15):5403.
[106]Goldsbury, C.; Kistler, J.; Aebi, U.; Arvinte, T.; Cooper, G. J., Watching amyloid fibrils grow by time-lapse atomic force microscopy. Journal of molecular biology.1999, 285(1):33-39.
[107]Harper, J.D.; Lieber, C. M.; Lansbury Jr, P. T., Atomic force microscopic imaging of seeded fibril formation and fibril branching by the Alzheimer's disease amyloid-β protein. Chemistry & Biology.1997,4(12):951-959.
[108]Liu, R.; McAllister, C.; Lyubchenko, Y.; Sierks, M. R., Residues 17-20 and 30-35 of β-amyloid play critical roles in aggregation. Journal of neuroscience research.2004,75(2): 162-171.
[109]Loo, D. T.; Copani, A.; Pike, C. J.; Whittemore, E. R.; Walencewicz, A. J.; Cotman, C. W., Apoptosis is induced by beta-amyloid in cultured central nervous system neurons. Proceedings of the National Academy of Sciences.1993,90(17):7951-7955.
[110]Torok, M.; Abid, M.; Mhadgut, S. C.; Torok, B., Organofluorine inhibitors of amyloid fibrillogenesis. Biochemistry.2006,45(16):5377-5383.
[111]Chen, G.; Chen, K. S.; Knox, J.; Inglis, J.; Bernard, A.; Martin, S. J.; Justice, A.; McConlogue, L.; Games, D.; Freedman, S. B., A learning deficit related to age and β-amyloid plaques in a mouse model of Alzheimer's disease. Nature.2000,408(6815):975-979.
[112]Mattson, M. P.; Cheng, B.; Davis, D.; Bryant, K.; Lieberburg, I.; Rydel, R. E., β-Amyloid peptides destabilize calcium homeostasis and render human cortical neurons vulnerable to excitotoxicity. The journal of neuroscience.1992,12(2):376-389.
[113]Ma, X. J.; Liu, L.; Mao, X. B.; Niu, L.; Deng, K.; Wu, W. H.; Li, Y. M.; Yang, Y. L.; Wang, C., Amyloid p (1-42) folding multiplicity and single-molecule binding behavior studied with STM. Journal of molecular biology.2009,388(4):894-901.
[114]Losic, D.; Martin, L. L.; Mechler, A.; Aguilar, M.-I.; Small, D. H., High resolution scanning tunnelling microscopy of the β-amyloid protein (Aβ1-40) of Alzheimer's disease suggests a novel mechanism of oligomer assembly. Journal of Structural Biology.2006, 155(1):104-110.
[115]Cukalevski, R.; Boland, B.; Frohm, B.; Thulin, E.; Walsh, D.; Linse, S., Role of Aromatic Side Chains in Amyloid β-Protein Aggregation. ACS Chemical Neuroscience.2012, 3(12):1008-1016.
[116]Fasman, G.; Perczel, A.; Moore, C., Solubilization of β-amyloid-(1-42)-peptide: reversing the beta-sheet conformation induced by aluminum with silicates. Proceedings of the National Academy of Sciences.1995,92(2):369-371.
[117]Park, S.-Y.; Kim, D. S., Discovery of Natural Products from Curcuma 1 onga that Protect Cells from β-Amyloid Insult:A Drug Discovery Effort against Alzheimer's Disease. Journal of natural products.2002,65(9):1227-1231.
[118]Choo, L.-P. i.; Wetzel, D. L.; Halliday, W. C.; Jackson, M.; LeVine, S. M.; Mantsch, H. H., In situ characterization of beta-amyloid in Alzheimer's diseased tissue by synchrotron Fourier transform infrared microspectroscopy. Biophysical Journal.1996,71(4):1672-1679.
[119]Zhuang, W.; Sgourakis, N. G.; Li, Z.; Garcia, A. E.; Mukamel, S., Discriminating early stage Aβ42 monomer structures using chirality-induced 2DIR spectroscopy in a simulation study. Proceedings of the National Academy of Sciences of United States of America.2010, 107(36):15687-15692.
[120]Huang, T.; Yang, D.-S.; Plaskos, N. P.; Go, S.; Yip, C. M.; Fraser, P. E.; Chakrabartty, A., Structural studies of soluble oligomers of the Alzheimer β-amyloid peptide. Journal of molecular biology.2000,297(1):73-87.
[121]Gorman, P. M.; Yip, C. M.; Fraser, P. E.; Chakrabartty, A., Alternate aggregation pathways of the Alzheimer β-amyloid peptide:Aβ association kinetics at endosomal pH. Journal of molecular biology.2003,325(4):743-757.
[122]Voiciuk, V.; Valincius, G.; Budvytyte, R.; Matijoska, A.; Matulaitiene, I.; Niaura, G., Surface-enhanced Raman spectroscopy for detection of toxic amyloid β oligomers adsorbed on self-assembled monolayers. Spectrochimica Acta Part A:Molecular and Biomolecular Spectroscopy.2012,95:526-532.
[123]Tycko, R., Solid state NMR studies of amyloid fibril structure. Annual review of physical chemistry.2011,62:279.
[124]Kirschner, D. A.; Abraham, C.; Selkoe, D. J., X-ray diffraction from intraneuronal paired helical filaments and extraneuronal amyloid fibers in Alzheimer disease indicates cross-beta conformation. Proceedings of the National Academy of Sciences of the United States of Amercia.1986,83(2):503-507.
[125]Sunde, M.; Serpell, L. C.; Bartlam, M.; Fraser, P. E.; Pepys, M. B.; Blake, C. C. F., Common core structure of amyloid fibrils by synchrotron X-ray diffractionl. Journal of molecular biology.1997,273(3):729-739.
[126]Sanan, D.; Weisgraber, K.; Russell, S.; Mahley, R.; Huang, D.; Saunders, A.; Schmechel, D.; Wisniewski, T.; Frangione, B.; Roses, A., Apolipoprotein E associates with beta amyloid peptide of Alzheimer's disease to form novel monofibrils. Isoform apoE4 associates more efficiently than apoE3. Journal of Clinical Investigation.1994,94(2):860.
[127]Bartolini, M.; Bertucci, C.; Cavrini, V.; Andrisano, V., P-Amyloid aggregation induced by human acetylcholinesterase:inhibition studies. Biochemical pharmacology.2003,65(3): 407-416.
[128]Toyama, B. H.; Weissman, J. S., Amyloid structure:conformational diversity and consequences. Annual review of biochemistry.2011,80:557-585.
[129]Shen, C.-L.; Scott, G. L.; Merchant, F.; Murphy, R. M., Light scattering analysis of fibril growth from the amino-terminal fragment (1-28) of β-amyloid peptide. Biophysical Journal. 1993,65(6):2383-2395.
[130]Petkova, A. T.; Ishii, Y.; Balbach, J. J.; Antzutkin, O. N.; Leapman, R. D.; Delaglio,F.; Tycko, R., A structural model for Alzheimer's P-amyloid fibrils based on experimental constraints from solid state NMR. Proceedings of the National Academy of Sciences of the United States of Amercia.2002,99(26):16742.
[131]Makin, O.S.; Serpell L. C, Structures for amyloid fibrils. Febs Journal.2005,272(23): 5950-5961.
[132]Lesne, S.; Koh, M. T.; Kotilinek, L.; Kayed, R.; Glabe, C. G.; Yang, A.; Gallagher, M.; Ashe, K. H., A specific amyloid-β protein assembly in the brain impairs memory. Nature, 2006.440(7082):352-357.
[133]Giurleo, J. T.; He, X.; alaga D. S., P-Lactoglobulin assembles into amyloid through sequential aggregated intermediates. Journal of molecular biology.2008,381(5):1332-1348.
[134]Liihrs, T.; Ritter, C.; Adrian, M.; Riek-Loher, D.; Bohrmann, B.; Dobeli, H.; Schubert, D.; Riek, R.,3D structure of Alzheimer's amyloid-β (1-42) fibrils. Proceedings of the National Academy of Sciences of the United States of America.2005,102(48):17342-17347.
[135]Cheng, P.-N.; Liu, C.; Zhao, M.; Eisenberg, D.; Nowick, J. S., Amyloid β-sheet mimics that antagonize protein aggregation and reduce amyloid toxicity. Nature Chemistry.2012, 4(11):927-933.
[136]Puchtler, H.; Sweat, F.; Levine, M., On the binding of Congo red by amyloid. Journal of Histochemistry & Cytochemistry.1962,10(3):355-364.
[137]Lendel, C.; Bolognesi, B.; Wahlstrom, A.; Dobson, C. M.; Graslund, A., Detergent-like Interaction of Congo Red with the Amyloid β Peptide. Biochemistry.2010,49(7):1358-1360.
[138]Frid, P.; Anisimov, S. V.; Popovic, N., Congo red and protein aggregation in neurodegenerative diseases. Brain research reviews.2007,53(1):135-160.
[139]Lorenzo, A.; Yankner, B. A., P-amyloid neurotoxicity requires fibril formation and is inhibited by congo red. Proceedings of the National Academy of Sciences of the United States of Amercia.1994,91(25):12243-12247.
[140]Li, J.; Xiao, H.; Li, J.; Zhong, Y., Drug carrier systems based on water-soluble cationic β-cyclodextrin polymers. International Journal of Pharmaceutics.2004,278(2):329-342.
[141]Matsue, T.; Evans, D. H.; Osa, T.; Kobayashi, N., Electron-transfer reactions associated with host-guest complexation. Oxidation of ferrocenecarboxylic acid in the presence of. β-cyclodextrin. Journal of the American Chemical Society.1985,107(12):3411-3417.
[142]Del Valle, E. M., Cyclodextrins and their uses:a review. Process Biochemistry.2004, 39(9):1033-1046.
[143]Wang, M. S.; Boddapati, S.; Sierks, M. R., Cyclodextrins promote protein aggregation posing risks for therapeutic applications. Biochemical and Biophysical Research Communications.2009,386(3):526-531.
[144]Yang, C.; Zhu, X. L.; Li, J. Y.; Chen, K., Molecular dynamics simulation study on conformational behavior of A beta(1-40) and A beta(1-42) in water and methanol. Journal of Molecular Structure-Theochem.2009,907(1-3):51-56.
[145]Chu, J.; Gonzalez-Lopez, M.; Cockroft, S. L.; Amorin, M.; Ghadiri, M. R., Real-Time Monitoring of DNA Polymerase Function and Stepwise Single-Nucleotide DNA Strand Translocation through a Protein Nanopore. Angewandte Chemie International Edition.2010, 122(52):10304-10307.
[146]Scott, D.W., On optimal and data-based histograms. Biometrika,1979.66(3):605-610.
[147]Meller, A.; Nivon, L.; Brandin, E.; Golovchenko, J.; Branton, D., Rapid nanopore discrimination between single polynucleotide molecules. Proceedings of the National Academy of Sciences of the United States of America.2000,97(3):1079-1084.
[148]Schmittschmitt, J. P.; Scholtz, J. M., The role of protein stability, solubility, and net charge in amyloid fibril formation. Protein Science.2003,12(10):2374-2378.
[149]Tjernberg, L. O.; Callaway, D. J.; Tjernberg, A.; Hahne, S.; Lilliehook, C.; Terenius, L.; Thyberg, J.; Nordstedt, C., A molecular model of Alzheimer amyloid P-peptide fibril formation. Journal of Biological Chemistry.1999,274(18):12619-12625.
[150]Gu, L.; Braha, O.; Conlan, S.; Cheley, S.; Bayley, H., Stochastic sensing of organic analytes by a pore-forming protein containing a molecular adapter. Nature.1999.398(6729): 686-690.
[151]Polymeropoulos, M. H.; Lavedan, C.; Leroy, E.; Ide, S. E.; Dehejia, A.; Dutra, A.; Pike, B.; Root, H.; Rubenstein, J.; Boyer, R.,Mutation in the a-synuclein gene identified in families with Parkinson's disease. Science.1997,276(5321):2045-2047.
[152]Khurana, R.; Ionescu-Zanetti, C.; Pope, M.; Li, J.; Nielson, L.; Ramirez-Alvarado, M.; Regan, L.; Fink, A. L.; Carter, S. A., A general model for amyloid fibril assembly based on morphological studies using atomic force microscopy. Biophysical Journal.2003,85(2): 1135-1144.
[153]Weinreb, P. H.; Zhen, W.; Poon, A. W.; Conway, K. A.; Lansbury Jr, P. T, NACP, a protein implicated in Alzheimer's disease and learning, is natively unfolded. Biochemistry. 1996,35(43):13709-13715.
[154]Sharma, N.; Hewett, J.; Ozelius, L. J.; Ramesh, V.; McLean, P. J.; Breakefield, X. O.; Hyman, B. T., A close association of torsinA and a-synuclein in lewy bodies:a fluorescence resonance energy transfer study. The American journal of pathology.2001,159(1):339-344.
[155]Dusa, A.; Kaylor, J.; Edridge, S.; Bodner, N.; Hong, D.-F.; Fink, A. L., Characterization of oligomers during a-synuclein aggregation using intrinsic tryptophan fluorescence. Biochemistry.2006,45(8):2752-2760.
[156]Li, J.; Uversky, V. N.; Fink, A. L., Effect of familial Parkinson's disease point mutations A30P and A53T on the structural properties, aggregation, and fibrillation of human a-synuclein. Biochemistry.2001,40(38):11604-11613.
[157]Uversky, V. N.; Gillespie, J. R.; Fink, A. L., Why are "natively unfolded" proteins unstructured under physiologic conditions? Proteins:Structure, Function, and Bioinformatics. 2000,41(3):415-427.
[158]Giehm, L.; Oliveira, C. L. P.; Christiansen, G.; Pedersen, J. S.; Otzen, D. E., SDS-induced fibrillation of a-synuclein:an alternative fibrillation pathway. Journal of molecular biology.2010,401(1):115-133.
[159]Uversky, V. N., Evidence for a Partially Folded Intermediate in a-Synuclein Fibril Formation. Journal of Biological Chemistry.2001,276(14):10737-10744.
[160]Anderson, V. L.; Ramlall, T. F.; Rospigliosi, C. C.; Webb, W. W; Eliezer, D., Identification of a helical intermediate in trifluoroethanol-induced a-synuclein aggregation. Proceedings of the National Academy of Sciences of the United States of America.2010, 107(44):18850-18855.
[161]Wood, S. J.; Wypych, J.; Steavenson, S.; Louis, J.-C.; Citron, M.; Biere, A. L. α-Synuclein Fibrillogenesis Is Nucleation-dependent implications for the pathogenesis of Parkinson's disease. Journal of Biological Chemistry.1999,274(28):19509-19512.
[162]Lansbury, P. T., Evolution of amyloid:what normal protein folding may tell us about fibrillogenesis and disease. Proceedings of the National Academy of Sciences of the United States of America.1999,96(7):3342-3344.
[163]Eliezer, D.; Kutluay, E.; Bussell, R.; Browne, G., Conformational properties of a-synuclein in its free and lipid-associated states. Journal of molecular biology.2001,307(4): 1061-1073.
[164]Crowe, J. H.; Crowe, L. M.; Chapman, D., Preservation of membranes in anhydrobiotic organisms:the role of trehalose. Science (New York, NY).1984,223(4637):701.
[165]Liu, R.; Barkhordarian, H.; Emadi, S.; Park, C.; Sierks, M., Trehalose differentially inhibits aggregation and neurotoxicity of beta-amyloid 40 and 42. Neurobiology of Disease. 2005,20(1):74-81.
[166]Yu, W.-B.; Jiang, T.; Lan, D.-M.; Lu, J.-H.; Yue, Z.-Y.; Zhou, P.; Wang, J., Trehalose inhibits fibrillation of A53T mutant a-synuclein and disaggregates existing fibrils. Archives of Biochemistry and Biophysics.2012,523,144-150.
[167]Wolfe, A. J.; Mohammad; Cheley, S.; Bayley, H.; Movileanu, L., Catalyzing the translocation of polypeptides through attractive interactions. Journal of the American Chemical Society.2007,129(45):14034-14041.
[168]Arora, A.; Ha, C.; Park, C. B., Inhibition of insulin amyloid formation by small stress molecules. FEBS letters.2004,564(1):121-125.
[169]Tanaka, M.; Machida, Y.; Niu, S.; Ikeda, T.; Jana, N. R.; Doi, H.; Kurosawa, M.; Nekooki, M.; Nukina, N., Trehalose alleviates polyglutamine-mediated pathology in a mouse model of Huntington disease. Nature Medicine.2004,10(2):148-154.
[170]Sarkar, S.; Davies, J. E.; Huang, Z.; Tunnacliffe, A.; Rubinsztein, D. C., Trehalose, a novel mTOR-independent autophagy enhancer, accelerates the clearance of mutant huntingtin and α-synuclein. Journal of Biological Chemistry.2007,282(8):5641-5652.
[171]Besseling, N.; Lyklema, J., Molecular thermodynamics of hydrophobic hydration. The Journal of Physical Chemistry B.1997,101(38):7604-7611.
[172]Majd, S.; Yusko, E. C.; Billeh, Y. N.; Macrae, M. X.; Yang, J.; Mayer, M.; Applications of biological pores in nanomedicine, sensing, and nanoelectronics. Current Opinion in Biotechnology.2010,21 (4),439-476.
[173]Dgany, O.; Gonzalez, A.; Sofer, O.; Wang, W.; Zolotnitsky, G.; Wolf, A.; Shoham, Y.; Altman, A.; Wolf, S. G.; Shoseyov, O., The structural basis of the thermostability of SP1, a novel plant (Populus tremula) boiling stable protein. Journal of Biological Chemistry.2004, 279(49):51516-51523.
[174]Qin, L. X.; Li, Y.; Li, D. W.; Jing, C.; Chen, B. Q.; Ma, W.; Heyman, A.; Shoseyov, O.; Willner, I.; Tian, H., Electrodeposition of Single-Metal Nanoparticles on Stable Protein 1 Membranes:Application of Plasmonic Sensing by Single Nanoparticles. Angewandte Chemie International Edition.2012,51(1):140-144.
[175]Wang, W. X.; Dgany, O.; Wolf, S. G.; Levy, I.; Algom, R.; Pouny, Y.; Wolf, A.; Marton, I.; Altman, A.; Shoseyov, O., Aspen SP1, an exceptional thermal, protease and detergent resistant self-assembled nano-particle. Biotechnology and bioengineering.2006,95(1): 161-168.
[176]Khoutorsky, A.; Heyman, A.; Shoseyov, O.; Spira, M. E., Formation of Hydrophilic Nanochannels in the Membrane of Living Cells by the Ringlike Stable Protein-SPl. Nano Letters.2011,11(7):2901-2904.
[177]Kang, X.; Cheley, S.; Guan, X.; Bayley, H., Stochastic detection of enantiomers. Journal of the American Chemical Society,2006.128(33):10684-10685.
[178]Wang, W. X.; Pelah, D.; Alergand, T.; Shoseyov, O.; Altman, A., Characterization of SP1, a stress-responsive, boiling-soluble, homo-oligomeric protein from aspen. Plant physiology.2002,130(2):865-875.
[179]Henrickson, S. E.; DiMarzio, E. A.; Wang, Q.; Stanford, V. M.; Kasianowicz, J. J., Probing single nanometer-scale pores with polymeric molecular rulers. The Journal of chemical physics.2010,132(13):135101.
[180]Wang, Y.; Zheng, D.; Tan, Q.; Wang, M. X.; Gu, L. Q.,Nanopore-based detection of circulating microRNAs in lung cancer patients. Nature nanotechnology.2011,6(10):668-674.
[2]Neher, E.; Sakmann, B.; Steinbach, J. H., The extracellular patch clamp:a method for resolving currents through individual open channels in biological membranes. Pflugers Archiv.1978,375(2):p.219-228.
[3]Hamill, O.; Marty, A.; Neher, E.; Sakmann, B.; Sigworth, F., Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Archiv 1981,391 (2),85-100.
[4]http://www.nobelprize.org/nobel_prizes/medicine/laureates/1991/sakmann-autobio.html
[5]Bull, B.; Schneiderman, M.; Brecher, G., Platelet counts with the coulter counter. American Journal of Clinical Pathology.1965,44(6):678.
[6]McNally, B., Next generation nanopore-based DNA sequencing.2012, Boston University.
[7]Schadt, E.E.; Turner, S.; Kasarskis, A., A window into third-generation sequencing. Human Molecular Genetics.2010,19(R2):R227-R240.
[8]Branton, D.; Deamer, D. W.; Marziali, A.; Bayley, H.; Benner, S. A.; Butler, T.; Di Ventra, M.; Garaj, S.; Hibbs, A.; Huang, X. H.; Jovanovich, S. B.; Krstic, P. S.; Lindsay, S.; Ling, X. S. S.; Mastrangelo, C. H.; Meller, A.; Oliver, J. S.; Pershin, Y. V.; Ramsey, J. M.; Riehn, R.; Soni, G. V.; Tabard-Cossa, V.; Wanunu, M.; Wiggin, M.; Schloss, J. A., The potential and challenges of nanopore sequencing. Nature Biotechnology.2008,26(10):1146-1153.
[9]Gu, L.; Cheley, S.; Bayley, H., Capture of a single molecule in a nanocavity. Science. 2001,291(5504):636.
[10]Kang, X. F.; Cheley, S.; Rice-Ficht, A. C.; Bayley, H., A storable encapsulated bilayer chip containing a single protein nanopore. Journal of the American Chemical Society.2007, 129(15):4701-4705.
[11]White, R.; Ervin, E.; Yang, T.; Chen, X.; Daniel, S.; Cremer, P.; White, H., Single ion-channel recordings using glass nanopore membranes. Journal of the American Chemical Society,2007.129(38):11766-11775.
[12]Shim, J.; Gu, L., Stochastic sensing on a modular chip containing a single-ion channel.Analtical Chemistry.2007,79(6):2207-2213.
[13]Zhang, B.; Galusha, J.; Shiozawa, P.; Wang, G.; Bergren, A.; Jones, R.; White, R.; Ervin, E.; Cauley, C.; White, H., Bench-top method for fabricating glass-sealed nanodisk electrodes, glass nanopore electrodes, and glass nanopore membranes of controlled size. Analytical Chemistry.2007,79(13):4778-4787.
[14]Kasianowicz, J.J.; Bezrukov, S. M., Protonation dynamics of the a-toxin ion channel from spectral analysis of pH-dependent current fluctuations. Biophysical Journal.1995,69(1): 94-105.
[15]Movileanu, L.; Cheley, S.; Howorka, S.; Braha, O.; Bayley, H., Location of a constriction in the lumen of a transmembrane pore by targeted covalent attachment of polymer molecules. Journal of General Physiology.2001,117(3):239-251.
[16]Braha, O.; Gu, L. Q.; Zhou, L.; Lu, X.; Cheley, S.; Bayley, H., Simultaneous stochastic sensing of divalent metal ions. Nature Biotechnology.2000,18(9):1005-1007.
[17]Guan, X.; Gu, I... Q.; Cheley, S.; Braha, O.; Bayley, H., Stochastic sensing of TNT with a genetically engineered pore. Chembiochem.2005,6(10):1875-1881.
[18]Howorka, S.; Movileanu, L.; Braha, O.; Bayley, H., Kinetics of duplex formation for individual DNA strands within a single protein nanopore. Proceedings of the National Academy of Sciences of the United States of America.2001,98(23):12996-13001.
[19]Howorka, S.; Cheley, S.; Bayley, H., Sequence-specific detection of individual DNA strands using engineered nanopores. Nature Biotechnology.2001,19(7):636-639.
[20]Howorka, S.; Movileanu, L.; Lu, X.; Magnon, M.; Cheley, S.; Braha, O.; Bayley, H., A protein pore with a single polymer chain tethered within the lumen. Journal of the American Chemical Society.2000,122(11):2411-2416.
[21]Gu, L.-Q.; Bayley,H., Interaction of the Noncovalent Molecular Adapter, β-Cyclodextrin, with the Staphylococcal a-Hemolysin Pore. Biophysical Journal.2000,79(4):1967-1975.
[22]Stoddart, D.; Heron, A. J.; Mikhailova, E.; Maglia, G.; Bayley, H., Single-nucleotide discrimination in immobilized DNA oligonucleotides with a biological nanopore. Proceedings of the National Academy of Sciences of the United States of America.2009,106(19): 7702-7707.
[23]Clarke, J.; Wu, H. C.; Jayasinghe, L.; Patel, A.; Reid, S.; Bayley, H., Continuous base identification for single-molecule nanopore DNA sequencing. Nature nanotechnology.2009, 4(4):265-270.
[24]Cherf, G. M.; Lieberman, K. R.; Rashid, H.; Lam, C. E.; Karplus, K.; Akeson, M., Automated forward and reverse ratcheting of DNA in a nanopore at 5-A precision. Nature Biotechnology.2012,30(4):344-348.
[25]Lieberman, K. R.; Cherf, G. M.; Doody, M. J.; Olasagasti, F.; Kolodji, Y.; Akeson, M., Processive replication of single DNA molecules in a nanopore catalyzed by phi29 DNA polymerase. Journal of the American Chemical Society.2010,132(50):17961-17972.
[26]Faller, M., The Structure of a Mycobacterial Outer-Membrane Channel. Science.2004, 303(5661):1189-1192.
[27]Butler, T.; Pavlenok, M.; Derrington, I.; Niederweis, M.; Gundlach, J., Single-molecule DNA detection with an engineered MspA protein nanopore. Proceedings of the National Academy of Sciences.2008,105(52):20647-20652.
[28]Derrington, I. M.; Butler, T. Z.; Collins, M. D.; Manrao, E.; Pavlenok, M.; Niederweis, M.; Gundlach, J. H., Nanopore DNA sequencing with MspA. Proceedings of the National Academy of Sciences.2010,107(37):16060-16065.
[29]Manrao, E. A.; Derrington, I. M.; Laszlo, A. H.; Langford, K. W.; Hopper, M. K.; Gillgren, N.; Pavlenok, M.; Niederweis, M.; Gundlach, J. H., Reading DNA at single-nucleotide resolution with a mutant MspA nanopore and phi29 DNA polymerase. Nature Biotechnology.2012,30(4):349-353.
[30]Wendell, D.; Jing, P.; Geng, J.; Subramaniam, V.; Lee, T. J.; Montemagno, C.; Guo, P., Translocation of double-stranded DNA through membrane-adapted phi29 motor protein nanopores. Nature nanotechnology.2009,4(11):765-772.
[31]Movileanu, L.; Bayley, H., Peptide binding to a transmembrane protein pore. Biophysical Journal.2005,88(1):552A-552A.
[32]Movileanu, L.; Howorka, S.; Braha, O.; Bayley, H., Detecting protein analytes that modulate transmembrane movement of a polymer chain within a single protein pore. Nature Biotechnology.2000,18(10):1091-1095.
[33]Movileanu, L., Interrogating single proteins through nanopores:challenges and opportunities. Trends in Biotechnology.2009,27(6):333-341.
[34]Movileanu, L.; Schmittschmitt, J. P.; Scholtz, J. M.; Bayley, H., Interactions of peptides with a protein pore. Biophysical Journal.2005,89(2):1030-1045.
[35]Okuyama, K.; Hongo, C.; Fukushima, R.; Wu, G.; Narita, H.; Noguchi, K.; Tanaka, Y.; Nishino, N., Crystal structures of collagen model peptides with Pro-Hyp-Gly repeating sequence at 1.26 resolution:Implications for proline ring puckering. Peptide Science.2004, 76(5):367-377.
[36]Sutherland, T. C.; Long, Y. T.; Stefureac, R. I.; Bediako-Amoa, I.; Kraatz, H. B.; Lee, J. S., Structure of peptides investigated by nanopore analysis. Nano Letters.2004,4(7): 1273-1277.
[37]Long, Y.; Zhang, M., Self-assembling bacterial pores as components of nanobiosensors for the detection of single peptide molecules. Science in China Series B:Chemistry.2009, 52(6):731-733.
[38]Stefureac, R.; Long, Y.-T.; Kraatz, H.-B.; Howard, P.; Lee, J. S., Transport of a-Helical peptides through α-Hemolysin and aerolysin pores. Biochemistry.2006,45(30):9172-9179.
[39]Wolfe, A. J.; Mohammad; Cheley, S.; Bayley, H.; Movileanu, L., Catalyzing the Translocation of polypeptides through attractive interactions. Journal of the American Chemical Society.2007,129(45):14034-14041.
[40]Stefureac, R. I.; Lee, J. S., Nanopore analysis of the folding of zinc fingers. Small.2008, 4(10):1646-1650.
[41]Oukhaled, G.; Mathe, J.; Biance, A. L.; Bacri, L.; Betton, J. M.; Lairez, D.; Pelta, J.; Auvray, L., Unfolding of proteins and long transient conformations detected by single nanopore recording. Physical Review Letters.2007,98:15801.
[42]Stefureac, R.; Waldner, L.; Howard, P.; Lee, J. S., Nanopore analysis of a small 86-residue protein. Small.2008,4(1):59-63.
[43]Akeson, M.; Branton, D.; Kasianowicz, J.; Brandin, E.; Deamer, D., Microsecond time-scale discrimination among polycytidylic acid, polyadenylic acid, and polyuridylic acid as homopolymers or as segments within single RNA molecules. Biophysical Journal.1999, 77(6):3227-3233.
[44]David R.-L.; Bayley, H., Multistep protein unfolding during nanopore translocation. Nature nanotechnology.2013,8:288-295.
[45]Nivala, J.; Marks, D. B.; Akeson, M., Unfoldase-mediated protein translocation through an α-hemolysin nanopore. Nature Biotechnology.2013,31 (3),247-250.
[46]Song, L.; Hobaugh, M.; Shustak, C.; Cheley, S.; Bayley, U.; Gouaux, J., Structure of staphylococcal α-hemolysin, a heptameric transmembrane pore. Science.1996,274(5294): 1859-1866.
[47]Mohammad, M. M.; Prakash, S.; Matouschek, A.; Movileanu, L., Controlling a single protein in a nanopore through electrostatic traps. Journal of the American Chemical Society. 2008,130(12):4081-4088.
[48]Cockroft, S. L.; Chu, J.; Amorin, M.; Bayley, H.; Ghadiri, M. R., A single-molecule nanopore device detects DNA polymerase activity with single-nucleotide resolution. Journal of the American Chemical Society.2008,130(3):818-820.
[49]Cheley, S.; Xie, H. Z.; Bayley, H., A genetically encoded pore for the stochastic detection of a protein kinase. Chembiochem.2006,7(12):1923-1927.
[50]Bretscher, M.S., Asymmetrical lipid bilayer structure for biological membranes. Nature. 1972,236(61):11-12.
[51]Deamer, D., Nanopore analysis of nucleic acids bound to exonucleases and polymerases. Annual review of biophysics.2010,39:79-90.
[52]Kasianowicz, J. J.; Henrickson, S. E.; Weetall, H. H.; Robertson, B., Simultaneous multianalyte detection with a nanometer-scale pore. Analytical Chemistry.2001,73(10): 2268-2272.
[53]Hornblower, B.; Coombs, A.; Whitaker, R.; Kolomeisky, A.; Picone, S.; Meller, A.; Akeson, M., Single-molecule analysis of DNA-protein complexes using nanopores. Nature Methods.2007,4(4):315-318.
[54]Astier, Y.; Kainov, D. E.; Bayley, H.; Tuma, R.; Howorka, S., Stochastic detection of motor protein-RNA complexes by single-channel current recording. Chemphyschem.2007, 8(15):2189-2194.
[55]Adler, A.; Grossman, L.; Fasman, G., Single-stranded oligomers and polymers of cytidylic and 2'-deoxycytidylic acids:Comparative optical rotatory studies. Proceedings of the National Academy of Sciences of the United States of America.1967,57(2):23.
[56]Hurt, N.; Wang, H.; Akeson, M.; Lieberman, K., Specific Nucleotide binding and rebinding to individual DNA polymerase complexes captured on a nanopore. Journal of the American Chemical Society.2009,131(10):3772-3778.
[57]Benner, S.; Chen, R.; Wilson, N.; Abu-Shumays, R.; Hurt, N.; Lieberman, K.; Deamer, D.; Dunbar, W.; Akeson, M., Sequence-specific detection of individual DNA polymerase complexes in real time using a nanopore. Nature nanotechnology.2007,2(11):718.
[58]Wilson, N.; Abu-Shumays, R.; Gyarfas, B.; Wang, H.; Lieberman, K.; Akeson, M.; Dunbar, W., Electronic control of DNA polymerase binding and unbinding to single DNA molecules. Journal of the American Chemical Society.2009,131(10):3772-3778.
[59]Panwar, A.S.; Muthukumar, M., Enzyme-modulated DNA translocation through a nanopore. Journal of the American Chemical Society.2009,131(51):18563-18570.
[60]Cockroft, S.L.; Chu, J.; Amorin, M; Bayley, H.; Ghadiri, M. R., A single-molecule nanopore device detects DNA polymerase activity with single-nucleotide resolution. Journal of the American Chemical Society.2008,130(3):818-820.
[61]Prusiner, S.B.; Molecular biology of prion diseases. Science.1991,252(5012): 1515-1522.
[62]Masters, C. L.; Simms, G.; Weinman, N. A.; Multhaup, G.; McDonald, B. L.; Beyreuther, K., Amyloid plaque core protein in Alzheimer disease and down syndrome. Proceedings of the National Academy of Sciences of the United States of America.1985,82(12):4245-4249.
[63]Parkinson, J., An essay on the shaking palsy.1817:Printed by Whittingham and Rowland for Sherwood, Neely, and Jones. [64] Polymeropoulos, M. H.; Higgins, J. J.; Golbe, L. I.; Johnson, W. G.; Ide, S. E.; Di Iorio, G.; Sanges, G.; Stenroos, E. S.; Pho, L. T.; Schaffer, A. A., Mapping of a gene for Parkinson's disease to chromosome 4q21-q23. Science (New York, NY),1996.274(5290):1197.
[65]Mathe, J.; Visram, H.; Viasnoff, V.; Rabin, Y.; Meller, A., Nanopore unzipping of individual DNA hairpin molecules. Biophysical Journal.2004,87(5):3205-3212.
[66]Ma, L.; Cockroft, S. L., Biological nanopores for single-molecule biophysics. Chembiochem.2010,11(1):25-34.
[67]Howorka, S.; Siwy, Z., Nanopore analytics:sensing of single molecules. Chemical Society Reviews.2009,38(8):2360-2384.
[68]Comer, J.; Aksimentiev, A., Predicting the DNA sequence dependence of nanopore ion current using atomic-resolution brownian dynamics. The Journal of Physical Chemistry C. 2012,116,3376-3393.
[69]Kawano, R.; Schibel, A. E. P.; Cauley, C.; White, H. S., Controlling the translocation of single-stranded DNA through a-hemolysin ion channels using viscosity. Langmuir.2008, 25(2):1233-1237.
[70]Ayub, M; Bayley, H., Single molecule RNA base identification with a biological nanopore. Biophysical Journal.2012,102(3):429a.
[71]Butler, T. Z.; Gundlach, J. H.; Troll, M., Ionic current blockades from DNA and RNA molecules in the a-hemolysin nanopore. Biophysical Journal.2007,93(9):3229-3240.
[72]Deamer, D.; Branton, D., Characterization of nucleic acids by nanopore analysis. Account Chemistry Research.2002,35(10):817-825.
[73]Andreeva-Kovalevskaya, Z.; Solonin, A.; Sineva, E.; Ternovsky, V., Pore-forming proteins and adaptation of living organisms to environmental conditions. Biochemistry (Moscow).2008,73(13):1473-1492.
[74]Muthukumar, M., Polymer translocation through a hole. The Journal of chemical physics. 1999,111:10371.
[75]Muthukumar, M., Translocation of a confined polymer through a hole. Physical Review Letters.2001,86(14):3188-3191.
[76]Tropini, C; Marziali, A., Multi-nanopore force spectroscopy for DNA analysis. Biophysical Journal.2007,92(5):1632-1637.
[77]Hung, W.; Chen, F.; Huang, H. W., Order-disorder transition in bilayers of diphytanoyl phosphatidylcholine. Biochimica et Biophysica Acta (BBA)-Biomembranes.2000,1467(1): 198-206.
[78]Lindsey, H.; Petersen, N.; Chan, S. I., Physicochemical characterization of 1, 2-diphytanoyl-sn-glycero-3-phosphocholine in model membrane systems. Biochimica et Biophysica Acta (BBA)-Biomembranes.1979,555(1):147-167.
[79]Boheim, G; Hanke, W.; Eibl, H., Lipid phase transition in planar bilayer membrane and its effect on carrier-and pore-mediated ion transport. Proceedings of the National Academy of Sciences of the United States of America.1980,77(6):3403-3407.
[80]Morera, F. J.; Vargas, G.; Gonzalez, C.; Rosenmann, E.; Latorre, R., Ion-channel reconstitution, In Methods in Membrane Lipids.2007, Springer.571-585.
[81]Phillips, R.; Ursell, T.; Wiggins, P.; Sens, P., Emerging roles for lipids in shaping membrane-protein function. Nature.2009,459(7245):379-385.
[82]Miller, C., Ion channel reconstitution.1986, Springer.
[83]Niles, W.; Levis, R.; Cohen, F., Planar bilayer membranes made from phospholipid monolayers form by a thinning process. Biophysical Journal.1988,53(3):327-335.
[84]White, S.; Petersen, D.; Simon, S.; Yafuso, M., Formation of planar bilayer membranes from lipid monolayers. A critique. Biophysical Journal.1976,16(5):481-489.
[85]Montal, M.; Mueller, P., Formation of bimolecular membranes from lipid monolayers and a study of their electrical properties. Proceedings of the National Academy of Sciences of the United States of America.1972,69(12):3561-3566.
[86]Peterman, M. C.; Ziebarth, J. M.; Braha, O.; Bayley, H.; Fishman, H. A.; Bloom, D., Ion channels and lipid bilayer membranes under high potentials using microfabricated apertures. Biomedical Microdevices.2002,4(3):231-236.
[87]Kang, X.; Gu, L.; Cheley, S.; Bayley, H., Single protein pores containing molecular adapters at high temperatures. Angewandte Chemie International Edition.2005,44(10): 1495-1499.
[88]Wonderlin, W.; Finkel, A.; French, R., Optimizing planar lipid bilayer single-channel recordings for high resolution with rapid voltage steps. Biophysical Journal.1990,58(2): 289-297.
[89]Mayer, M.; Kriebel, J. K.; Tosteson, M. T.; Whitesides, G. M., Microfabricated teflon membranes for low-noise recordings of ion channels in planar lipid bilayers. Biophysical Journal.2003,85(4):2684-2695.
[90]Purves, R., Microelectrode methods for intracellular recording and ionophoresis.1981, 208.:Academic Press London, UK.
[91]Hamill, O.; Marty, A.; Neher, E.; Sakmann, B.; Sigworth, F., Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Archiv.1981,391(2):85-100.
[92]Smeets, R. M. M.; Keyser, U. F.; Dekker, N.F.; Dekker, C., Noise in solid-state nanopores. Proceedings of the National Academy of Sciences of the United States of America. 2008,105(2):417.
[93]Hughes, A. J.; Daniel, S. E.; Kilford, L.; Lees, A. J., Accuracy of clinical diagnosis of idiopathic Parkinson's disease:a clinico-pathological study of 100 cases. Journal of Neurology, Neurosurgery & Psychiatry.1992,55(3):181-184.
[94]Corder, E.; Saunders, A.; Strittmatter, W.; Schmechel, D.; Gaskell, P.; Small, G.; Roses, A.; Haines, J.; Pericak-Vance, M. A., Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science.1993,261(5123):921-923.
[95]Lue, L.-F.; Brachova, L.; Civin, H. W.; Rogers, J., Inflammation, A P-amyloid Deposition, and Neurofibrillary Tangle Formation as Correlates of Alzheimer's Disease Neurodegeneration. Journal of Neuropathology & Experimental Neurology.1996,55(10): 1083-1088.
[96]Benilova, I.; Karran, E.; Strooper, B. D., The toxic Aβ oligomer and Alzheimer's disease: an emperor in need of clothes. Nature Neuroscience.2012,15(3):349-357.
[97]de la Torre, J.C., Is Alzheimer's disease a neurodegenerative or a vascular disorder? Data, dogma, and dialectics. The Lancet Neurology.2004,3(3):184-190.
[98]Ross, C.A.; Poirier, M.A., Protein aggregation and neurodegenerative disease.2004.
[99]Tanzi, R. E.; St George-Hyslop, P. H.; Haines, J. L.; Polinsky, R. J.; Nee, L.; Foncin, J.-F.; Neve, R. L.; McClatchey, A. I.; Conneally, P. M.; Gusella, J. F., The genetic defect in familial Alzheimer's disease is not tightly linked to the amyloid p-protein gene. Nature.1987,329,156-157.
[100]Mullan, M.; Crawford, F.; Axelman, K.; Houlden, H.; Lilius, L.; Winblad, B.; Lannfelt, L., A pathogenic mutation for probable Alzheimer's disease in the APP gene at the N-terminus of β-amyloid. Nature genetics.1992,1(5):345-347.
[101]Kang, J.; Lemaire, H.-G.; Unterbeck, A.; Salbaum, J. M.; Masters, C. L.; Grzeschik, K.-H.; Multhaup, G.; Beyreuther, K.; Muller-Hill, B., The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. Nature.1987,325,733-736.
[102]Dries, D.R.; Yu, G.; Herz, J., Extracting β-amyloid from Alzheimer's disease. Proceedings of the National Academy of Sciences.2012,109(9):3199-3200.
[103]Datki, Z.; Papp, R.; Zadori, D.; Soos, K.; Fulop, L.; Juhasz, A.; Laskay, G.; Hetenyi, C.; Mihalik, E.; Zarandi, M.; Penke, B., In vitro model of neurotoxicity of A beta 1-42 and neuroprotection by a pentapeptide:irreversible events during the first hour. Neurobiology of Disease.2004,17(3):507-515.
[104]Seilheimer, B.; Bohrmann, B.; Bondolfi, L.; Muller, F.; Stuber, D.; Dobeli, H., The toxicity of the Alzheimer's [beta]-amyloid peptide correlates with a distinct fiber morphology. Journal of Structural Biology.1997,119(1):59-71.
[105]Xu, Y.; Shen, J.; Luo, X.; Zhu, W.; Chen, K.; Ma, J.; Jiang, H., Conformational transition of amyloid β-peptide. Proceedings of the National Academy of Sciences of the United States of America.2005,102(15):5403.
[106]Goldsbury, C.; Kistler, J.; Aebi, U.; Arvinte, T.; Cooper, G. J., Watching amyloid fibrils grow by time-lapse atomic force microscopy. Journal of molecular biology.1999, 285(1):33-39.
[107]Harper, J.D.; Lieber, C. M.; Lansbury Jr, P. T., Atomic force microscopic imaging of seeded fibril formation and fibril branching by the Alzheimer's disease amyloid-β protein. Chemistry & Biology.1997,4(12):951-959.
[108]Liu, R.; McAllister, C.; Lyubchenko, Y.; Sierks, M. R., Residues 17-20 and 30-35 of β-amyloid play critical roles in aggregation. Journal of neuroscience research.2004,75(2): 162-171.
[109]Loo, D. T.; Copani, A.; Pike, C. J.; Whittemore, E. R.; Walencewicz, A. J.; Cotman, C. W., Apoptosis is induced by beta-amyloid in cultured central nervous system neurons. Proceedings of the National Academy of Sciences.1993,90(17):7951-7955.
[110]Torok, M.; Abid, M.; Mhadgut, S. C.; Torok, B., Organofluorine inhibitors of amyloid fibrillogenesis. Biochemistry.2006,45(16):5377-5383.
[111]Chen, G.; Chen, K. S.; Knox, J.; Inglis, J.; Bernard, A.; Martin, S. J.; Justice, A.; McConlogue, L.; Games, D.; Freedman, S. B., A learning deficit related to age and β-amyloid plaques in a mouse model of Alzheimer's disease. Nature.2000,408(6815):975-979.
[112]Mattson, M. P.; Cheng, B.; Davis, D.; Bryant, K.; Lieberburg, I.; Rydel, R. E., β-Amyloid peptides destabilize calcium homeostasis and render human cortical neurons vulnerable to excitotoxicity. The journal of neuroscience.1992,12(2):376-389.
[113]Ma, X. J.; Liu, L.; Mao, X. B.; Niu, L.; Deng, K.; Wu, W. H.; Li, Y. M.; Yang, Y. L.; Wang, C., Amyloid p (1-42) folding multiplicity and single-molecule binding behavior studied with STM. Journal of molecular biology.2009,388(4):894-901.
[114]Losic, D.; Martin, L. L.; Mechler, A.; Aguilar, M.-I.; Small, D. H., High resolution scanning tunnelling microscopy of the β-amyloid protein (Aβ1-40) of Alzheimer's disease suggests a novel mechanism of oligomer assembly. Journal of Structural Biology.2006, 155(1):104-110.
[115]Cukalevski, R.; Boland, B.; Frohm, B.; Thulin, E.; Walsh, D.; Linse, S., Role of Aromatic Side Chains in Amyloid β-Protein Aggregation. ACS Chemical Neuroscience.2012, 3(12):1008-1016.
[116]Fasman, G.; Perczel, A.; Moore, C., Solubilization of β-amyloid-(1-42)-peptide: reversing the beta-sheet conformation induced by aluminum with silicates. Proceedings of the National Academy of Sciences.1995,92(2):369-371.
[117]Park, S.-Y.; Kim, D. S., Discovery of Natural Products from Curcuma 1 onga that Protect Cells from β-Amyloid Insult:A Drug Discovery Effort against Alzheimer's Disease. Journal of natural products.2002,65(9):1227-1231.
[118]Choo, L.-P. i.; Wetzel, D. L.; Halliday, W. C.; Jackson, M.; LeVine, S. M.; Mantsch, H. H., In situ characterization of beta-amyloid in Alzheimer's diseased tissue by synchrotron Fourier transform infrared microspectroscopy. Biophysical Journal.1996,71(4):1672-1679.
[119]Zhuang, W.; Sgourakis, N. G.; Li, Z.; Garcia, A. E.; Mukamel, S., Discriminating early stage Aβ42 monomer structures using chirality-induced 2DIR spectroscopy in a simulation study. Proceedings of the National Academy of Sciences of United States of America.2010, 107(36):15687-15692.
[120]Huang, T.; Yang, D.-S.; Plaskos, N. P.; Go, S.; Yip, C. M.; Fraser, P. E.; Chakrabartty, A., Structural studies of soluble oligomers of the Alzheimer β-amyloid peptide. Journal of molecular biology.2000,297(1):73-87.
[121]Gorman, P. M.; Yip, C. M.; Fraser, P. E.; Chakrabartty, A., Alternate aggregation pathways of the Alzheimer β-amyloid peptide:Aβ association kinetics at endosomal pH. Journal of molecular biology.2003,325(4):743-757.
[122]Voiciuk, V.; Valincius, G.; Budvytyte, R.; Matijoska, A.; Matulaitiene, I.; Niaura, G., Surface-enhanced Raman spectroscopy for detection of toxic amyloid β oligomers adsorbed on self-assembled monolayers. Spectrochimica Acta Part A:Molecular and Biomolecular Spectroscopy.2012,95:526-532.
[123]Tycko, R., Solid state NMR studies of amyloid fibril structure. Annual review of physical chemistry.2011,62:279.
[124]Kirschner, D. A.; Abraham, C.; Selkoe, D. J., X-ray diffraction from intraneuronal paired helical filaments and extraneuronal amyloid fibers in Alzheimer disease indicates cross-beta conformation. Proceedings of the National Academy of Sciences of the United States of Amercia.1986,83(2):503-507.
[125]Sunde, M.; Serpell, L. C.; Bartlam, M.; Fraser, P. E.; Pepys, M. B.; Blake, C. C. F., Common core structure of amyloid fibrils by synchrotron X-ray diffractionl. Journal of molecular biology.1997,273(3):729-739.
[126]Sanan, D.; Weisgraber, K.; Russell, S.; Mahley, R.; Huang, D.; Saunders, A.; Schmechel, D.; Wisniewski, T.; Frangione, B.; Roses, A., Apolipoprotein E associates with beta amyloid peptide of Alzheimer's disease to form novel monofibrils. Isoform apoE4 associates more efficiently than apoE3. Journal of Clinical Investigation.1994,94(2):860.
[127]Bartolini, M.; Bertucci, C.; Cavrini, V.; Andrisano, V., P-Amyloid aggregation induced by human acetylcholinesterase:inhibition studies. Biochemical pharmacology.2003,65(3): 407-416.
[128]Toyama, B. H.; Weissman, J. S., Amyloid structure:conformational diversity and consequences. Annual review of biochemistry.2011,80:557-585.
[129]Shen, C.-L.; Scott, G. L.; Merchant, F.; Murphy, R. M., Light scattering analysis of fibril growth from the amino-terminal fragment (1-28) of β-amyloid peptide. Biophysical Journal. 1993,65(6):2383-2395.
[130]Petkova, A. T.; Ishii, Y.; Balbach, J. J.; Antzutkin, O. N.; Leapman, R. D.; Delaglio,F.; Tycko, R., A structural model for Alzheimer's P-amyloid fibrils based on experimental constraints from solid state NMR. Proceedings of the National Academy of Sciences of the United States of Amercia.2002,99(26):16742.
[131]Makin, O.S.; Serpell L. C, Structures for amyloid fibrils. Febs Journal.2005,272(23): 5950-5961.
[132]Lesne, S.; Koh, M. T.; Kotilinek, L.; Kayed, R.; Glabe, C. G.; Yang, A.; Gallagher, M.; Ashe, K. H., A specific amyloid-β protein assembly in the brain impairs memory. Nature, 2006.440(7082):352-357.
[133]Giurleo, J. T.; He, X.; alaga D. S., P-Lactoglobulin assembles into amyloid through sequential aggregated intermediates. Journal of molecular biology.2008,381(5):1332-1348.
[134]Liihrs, T.; Ritter, C.; Adrian, M.; Riek-Loher, D.; Bohrmann, B.; Dobeli, H.; Schubert, D.; Riek, R.,3D structure of Alzheimer's amyloid-β (1-42) fibrils. Proceedings of the National Academy of Sciences of the United States of America.2005,102(48):17342-17347.
[135]Cheng, P.-N.; Liu, C.; Zhao, M.; Eisenberg, D.; Nowick, J. S., Amyloid β-sheet mimics that antagonize protein aggregation and reduce amyloid toxicity. Nature Chemistry.2012, 4(11):927-933.
[136]Puchtler, H.; Sweat, F.; Levine, M., On the binding of Congo red by amyloid. Journal of Histochemistry & Cytochemistry.1962,10(3):355-364.
[137]Lendel, C.; Bolognesi, B.; Wahlstrom, A.; Dobson, C. M.; Graslund, A., Detergent-like Interaction of Congo Red with the Amyloid β Peptide. Biochemistry.2010,49(7):1358-1360.
[138]Frid, P.; Anisimov, S. V.; Popovic, N., Congo red and protein aggregation in neurodegenerative diseases. Brain research reviews.2007,53(1):135-160.
[139]Lorenzo, A.; Yankner, B. A., P-amyloid neurotoxicity requires fibril formation and is inhibited by congo red. Proceedings of the National Academy of Sciences of the United States of Amercia.1994,91(25):12243-12247.
[140]Li, J.; Xiao, H.; Li, J.; Zhong, Y., Drug carrier systems based on water-soluble cationic β-cyclodextrin polymers. International Journal of Pharmaceutics.2004,278(2):329-342.
[141]Matsue, T.; Evans, D. H.; Osa, T.; Kobayashi, N., Electron-transfer reactions associated with host-guest complexation. Oxidation of ferrocenecarboxylic acid in the presence of. β-cyclodextrin. Journal of the American Chemical Society.1985,107(12):3411-3417.
[142]Del Valle, E. M., Cyclodextrins and their uses:a review. Process Biochemistry.2004, 39(9):1033-1046.
[143]Wang, M. S.; Boddapati, S.; Sierks, M. R., Cyclodextrins promote protein aggregation posing risks for therapeutic applications. Biochemical and Biophysical Research Communications.2009,386(3):526-531.
[144]Yang, C.; Zhu, X. L.; Li, J. Y.; Chen, K., Molecular dynamics simulation study on conformational behavior of A beta(1-40) and A beta(1-42) in water and methanol. Journal of Molecular Structure-Theochem.2009,907(1-3):51-56.
[145]Chu, J.; Gonzalez-Lopez, M.; Cockroft, S. L.; Amorin, M.; Ghadiri, M. R., Real-Time Monitoring of DNA Polymerase Function and Stepwise Single-Nucleotide DNA Strand Translocation through a Protein Nanopore. Angewandte Chemie International Edition.2010, 122(52):10304-10307.
[146]Scott, D.W., On optimal and data-based histograms. Biometrika,1979.66(3):605-610.
[147]Meller, A.; Nivon, L.; Brandin, E.; Golovchenko, J.; Branton, D., Rapid nanopore discrimination between single polynucleotide molecules. Proceedings of the National Academy of Sciences of the United States of America.2000,97(3):1079-1084.
[148]Schmittschmitt, J. P.; Scholtz, J. M., The role of protein stability, solubility, and net charge in amyloid fibril formation. Protein Science.2003,12(10):2374-2378.
[149]Tjernberg, L. O.; Callaway, D. J.; Tjernberg, A.; Hahne, S.; Lilliehook, C.; Terenius, L.; Thyberg, J.; Nordstedt, C., A molecular model of Alzheimer amyloid P-peptide fibril formation. Journal of Biological Chemistry.1999,274(18):12619-12625.
[150]Gu, L.; Braha, O.; Conlan, S.; Cheley, S.; Bayley, H., Stochastic sensing of organic analytes by a pore-forming protein containing a molecular adapter. Nature.1999.398(6729): 686-690.
[151]Polymeropoulos, M. H.; Lavedan, C.; Leroy, E.; Ide, S. E.; Dehejia, A.; Dutra, A.; Pike, B.; Root, H.; Rubenstein, J.; Boyer, R.,Mutation in the a-synuclein gene identified in families with Parkinson's disease. Science.1997,276(5321):2045-2047.
[152]Khurana, R.; Ionescu-Zanetti, C.; Pope, M.; Li, J.; Nielson, L.; Ramirez-Alvarado, M.; Regan, L.; Fink, A. L.; Carter, S. A., A general model for amyloid fibril assembly based on morphological studies using atomic force microscopy. Biophysical Journal.2003,85(2): 1135-1144.
[153]Weinreb, P. H.; Zhen, W.; Poon, A. W.; Conway, K. A.; Lansbury Jr, P. T, NACP, a protein implicated in Alzheimer's disease and learning, is natively unfolded. Biochemistry. 1996,35(43):13709-13715.
[154]Sharma, N.; Hewett, J.; Ozelius, L. J.; Ramesh, V.; McLean, P. J.; Breakefield, X. O.; Hyman, B. T., A close association of torsinA and a-synuclein in lewy bodies:a fluorescence resonance energy transfer study. The American journal of pathology.2001,159(1):339-344.
[155]Dusa, A.; Kaylor, J.; Edridge, S.; Bodner, N.; Hong, D.-F.; Fink, A. L., Characterization of oligomers during a-synuclein aggregation using intrinsic tryptophan fluorescence. Biochemistry.2006,45(8):2752-2760.
[156]Li, J.; Uversky, V. N.; Fink, A. L., Effect of familial Parkinson's disease point mutations A30P and A53T on the structural properties, aggregation, and fibrillation of human a-synuclein. Biochemistry.2001,40(38):11604-11613.
[157]Uversky, V. N.; Gillespie, J. R.; Fink, A. L., Why are "natively unfolded" proteins unstructured under physiologic conditions? Proteins:Structure, Function, and Bioinformatics. 2000,41(3):415-427.
[158]Giehm, L.; Oliveira, C. L. P.; Christiansen, G.; Pedersen, J. S.; Otzen, D. E., SDS-induced fibrillation of a-synuclein:an alternative fibrillation pathway. Journal of molecular biology.2010,401(1):115-133.
[159]Uversky, V. N., Evidence for a Partially Folded Intermediate in a-Synuclein Fibril Formation. Journal of Biological Chemistry.2001,276(14):10737-10744.
[160]Anderson, V. L.; Ramlall, T. F.; Rospigliosi, C. C.; Webb, W. W; Eliezer, D., Identification of a helical intermediate in trifluoroethanol-induced a-synuclein aggregation. Proceedings of the National Academy of Sciences of the United States of America.2010, 107(44):18850-18855.
[161]Wood, S. J.; Wypych, J.; Steavenson, S.; Louis, J.-C.; Citron, M.; Biere, A. L. α-Synuclein Fibrillogenesis Is Nucleation-dependent implications for the pathogenesis of Parkinson's disease. Journal of Biological Chemistry.1999,274(28):19509-19512.
[162]Lansbury, P. T., Evolution of amyloid:what normal protein folding may tell us about fibrillogenesis and disease. Proceedings of the National Academy of Sciences of the United States of America.1999,96(7):3342-3344.
[163]Eliezer, D.; Kutluay, E.; Bussell, R.; Browne, G., Conformational properties of a-synuclein in its free and lipid-associated states. Journal of molecular biology.2001,307(4): 1061-1073.
[164]Crowe, J. H.; Crowe, L. M.; Chapman, D., Preservation of membranes in anhydrobiotic organisms:the role of trehalose. Science (New York, NY).1984,223(4637):701.
[165]Liu, R.; Barkhordarian, H.; Emadi, S.; Park, C.; Sierks, M., Trehalose differentially inhibits aggregation and neurotoxicity of beta-amyloid 40 and 42. Neurobiology of Disease. 2005,20(1):74-81.
[166]Yu, W.-B.; Jiang, T.; Lan, D.-M.; Lu, J.-H.; Yue, Z.-Y.; Zhou, P.; Wang, J., Trehalose inhibits fibrillation of A53T mutant a-synuclein and disaggregates existing fibrils. Archives of Biochemistry and Biophysics.2012,523,144-150.
[167]Wolfe, A. J.; Mohammad; Cheley, S.; Bayley, H.; Movileanu, L., Catalyzing the translocation of polypeptides through attractive interactions. Journal of the American Chemical Society.2007,129(45):14034-14041.
[168]Arora, A.; Ha, C.; Park, C. B., Inhibition of insulin amyloid formation by small stress molecules. FEBS letters.2004,564(1):121-125.
[169]Tanaka, M.; Machida, Y.; Niu, S.; Ikeda, T.; Jana, N. R.; Doi, H.; Kurosawa, M.; Nekooki, M.; Nukina, N., Trehalose alleviates polyglutamine-mediated pathology in a mouse model of Huntington disease. Nature Medicine.2004,10(2):148-154.
[170]Sarkar, S.; Davies, J. E.; Huang, Z.; Tunnacliffe, A.; Rubinsztein, D. C., Trehalose, a novel mTOR-independent autophagy enhancer, accelerates the clearance of mutant huntingtin and α-synuclein. Journal of Biological Chemistry.2007,282(8):5641-5652.
[171]Besseling, N.; Lyklema, J., Molecular thermodynamics of hydrophobic hydration. The Journal of Physical Chemistry B.1997,101(38):7604-7611.
[172]Majd, S.; Yusko, E. C.; Billeh, Y. N.; Macrae, M. X.; Yang, J.; Mayer, M.; Applications of biological pores in nanomedicine, sensing, and nanoelectronics. Current Opinion in Biotechnology.2010,21 (4),439-476.
[173]Dgany, O.; Gonzalez, A.; Sofer, O.; Wang, W.; Zolotnitsky, G.; Wolf, A.; Shoham, Y.; Altman, A.; Wolf, S. G.; Shoseyov, O., The structural basis of the thermostability of SP1, a novel plant (Populus tremula) boiling stable protein. Journal of Biological Chemistry.2004, 279(49):51516-51523.
[174]Qin, L. X.; Li, Y.; Li, D. W.; Jing, C.; Chen, B. Q.; Ma, W.; Heyman, A.; Shoseyov, O.; Willner, I.; Tian, H., Electrodeposition of Single-Metal Nanoparticles on Stable Protein 1 Membranes:Application of Plasmonic Sensing by Single Nanoparticles. Angewandte Chemie International Edition.2012,51(1):140-144.
[175]Wang, W. X.; Dgany, O.; Wolf, S. G.; Levy, I.; Algom, R.; Pouny, Y.; Wolf, A.; Marton, I.; Altman, A.; Shoseyov, O., Aspen SP1, an exceptional thermal, protease and detergent resistant self-assembled nano-particle. Biotechnology and bioengineering.2006,95(1): 161-168.
[176]Khoutorsky, A.; Heyman, A.; Shoseyov, O.; Spira, M. E., Formation of Hydrophilic Nanochannels in the Membrane of Living Cells by the Ringlike Stable Protein-SPl. Nano Letters.2011,11(7):2901-2904.
[177]Kang, X.; Cheley, S.; Guan, X.; Bayley, H., Stochastic detection of enantiomers. Journal of the American Chemical Society,2006.128(33):10684-10685.
[178]Wang, W. X.; Pelah, D.; Alergand, T.; Shoseyov, O.; Altman, A., Characterization of SP1, a stress-responsive, boiling-soluble, homo-oligomeric protein from aspen. Plant physiology.2002,130(2):865-875.
[179]Henrickson, S. E.; DiMarzio, E. A.; Wang, Q.; Stanford, V. M.; Kasianowicz, J. J., Probing single nanometer-scale pores with polymeric molecular rulers. The Journal of chemical physics.2010,132(13):135101.
[180]Wang, Y.; Zheng, D.; Tan, Q.; Wang, M. X.; Gu, L. Q.,Nanopore-based detection of circulating microRNAs in lung cancer patients. Nature nanotechnology.2011,6(10):668-674.