神经传导介质小分子与Aβ的相互作用研究
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摘要
p-淀粉样多肽(amyloid β-peptide,Aβ)是阿尔茨海默病(Alzheimer's disease, AD)病理学特征——淀粉样斑块的主要成分,与AD的发生密切相关。作为传导神经突触信号的重要介质,Cu2+、多巴胺(dopamine, DA)、去甲肾上腺素(norepinephrine, NE)等小分子可与Ap发生作用,对脑部神经元产生不同的影响。为了深入理解Ap与神经传导介质小分子的相互作用对AD病理发展的影响,本论文分别研究了Cu2+、DA、NE与Ap相互作用的机制,获得了相关动力学参数,并初步探讨了相关体系在AD病理中的作用。本论文主要工作包括：
(1)获得Aβ-Cu2+络合物的解离常数是探讨AD治疗方案的基础之一,但现有文献报道中没有涉及到酸性条件下的Aβ-Cu2+解离常数。本论文采用表面等离子体激元共振(surface plasmon resonance,SPR)技术研究了酸性条件下Ap与Cu2+相互作用的动力学,发现随着溶液环境从中性(pH7.0)到弱酸性(pH4.0), Aβ-Cu2+的解离常数从3.5×10-8mol·L-1增大到8.7×10-3mol·L-1。通过定量检测-OH的产生量,发现酸性环境下Cu2+催化产生·OH的能力增强,毒性增大；随着pH的升高,Aβ结合Cu2+的能力增强,抑制了Cu2+催化产生·OH的反应,降低了其细胞毒性。
(2)溶剂的选择影响Ap-Cu2+解离常数的检测。通常认为Tris是检测Aβ-Cu2+解离常数的理想溶剂。但作为亲核试剂,Tris对Aβ/Cu2+相互作用的影响尚不清楚。本论文采用多种方法系统研究了不同环境条件下Tris对Aβ/Cu2+相互作用的影响。透射电镜和电喷雾电离质谱结果证明酸性条件下可形成Tris-Aβ-Cu2+三元络合物。采用SPR、紫外吸收光谱和电化学技术发现,Tris对Aβ/Cu2+相互作用的影响：Kd增大一个数量级；阻碍Ap与Cu2+之间的电荷迁移,减弱其相应的紫外吸收；Aβ-Cu2+的氧化电位正移。通过定量检测-OH的产生量发现,由于Tris对于Aβ络合Cu2+的反应有竞争作用,使Aβ1-42-Cu2+的解离常数增大,溶液中游离Cu2+增多,所以Tris溶液中-OH的产量增大。中性条件下Tris与Ap无相互作用,不利于三元络合物的生成。
(3)研究Ap与DA的相互作用机理可解释DA在Ap的毒性和AD的发展中所起的作用。采用SPR和电化学技术研究了亲水段Aβ1-16与DA相互作用的化学计量比、作用位点和Kd。结果显示：Aβ1-16与DA相互作用的化学计量比为1：1；DA的酚羟基与Ap的Tyr10结合；Kd为0.30μmpl·L-1。通过定量检测·OH的产生量发现,适当浓度的DA可以释放Aβ-Cu2+中的Cu2+,增大·OH的产生量,增强其细胞毒性。圆二色光谱数据初步说明,Ap与DA的相互作用有可能促进Aβ寡聚体的形成,加剧脑部的神经毒性。
(4)SPR和电化学研究显示NE与Ap的相互作用机制与DA/Aβ的相似：化学计量比为1：1；NE的酚羟基与Ap的Tyr10结合；Kd为0.25μmol·L-1。通过定量检测·OH的产生量发现,适当浓度的NE可以释放A(3-Cu2+中的Cu2+,促进·OH的产生。圆二色光谱数据初步说明,Ap与NE的相互作用可能会促进Ap寡聚体的形成,加剧脑部局部区域的神经毒性。
A(3is the major constitute of senile plaque, a hallmark in the brain of AD victims. It is well-known that Aβ is crucial for the development of AD. The interactions of Aβ with neurotransmitters (Cu DA and NE) may affect the neuron. And the interactions of A(3with Cu2+DA and NE are very important for the neurobiological processes and pathogenesis of AD, therefore, the mechanisms of A(3interacting with Cu2+, DA and NE are investigated to get the kinetic constants, and the roles of A(3interacting with Cu2+, DA and NE in the pathogenesis of AD are discussed preliminarily. Base on the above considerations, the following studies were carried out.
(1) Interactions of Aβ with Cu2+are known to be pH-dependent and believed to play a crucial role in the neurotoxicity of AD. However, there is no reports about the affinity of Aβ-Cu2+under acidic pH. In this study, SPR sensor with immobilized Aβ was used to investigate the formation of Aβ-Cu2+complexes under acidic pH conditions. Dissociation constants (Kd) were calculated and shown to be pH-dependent, ranging from8.7×10-3to3.5×10-8mol·L-1under pH4.0-7.0. The physiological significance of Kd was preliminarily investigated by monitoring the generation of·OH in aerobic solutions containing Aβ-Cu2+and Cu2+. The results imply that acidic conditions could aggravate the oxidative stress in the presence of Cu2+, and the weak affinities of Aβ-Cu2+under acidic pH could further enhance the oxidative damage. However, under mildly acidic pH conditions, the formation of Ap-Cu2+reduced free Cu2+, inhibited the generation of·OH. In biological milieu, Aβ could protect neuron from oxidative stress.
(2) Numerous studies in the recent ten years show a large variation on the dissociation constant of Aβ-Cu2+under different solvent conditions. Among the common buffers, Tris is considered to be the most reliable. However, Tris is rich of nucleophilic groups, so it may have a more diversified role in the interaction of Aβ with Cu2+. Under acidic conditions, a Tris-Aβ-Cu2+ternary complex was identified using ESI-MS and TEM. The results of surface plasmon resonance reveal that the formation of a ternary complex increases the dissociation constant by almost one order of magnitude. Consequently, toxicity assessment indicates that the generation of-OH induced by the Aβ-Cu2+complex is enhanced in the presence of Tris. Increased pH condition disfavors the formation of Tris-Ap-Cu2+complex.
(3) Due to the controversial effects of DA on the toxicity of Aβ and the development of AD, it is necessary to understand the interaction of Aβ with DA. In this study, the stoichiometric ratio (1:1), binding site (Tyr10) and dissociation constant (KA=0.30μmol·L-1) of DA interacting with Aβ1-16were revealed. The physiological significance of Kd was investigated by monitoring the generation of·OH in aerobic solutions containing Cu2+. The results demonstrat that DA inhibits the interaction of Aβ with Cu2+, enhances the generation of-OH. The CD results preliminarily imply that DA may improve the formation of Aβ oligomer, and then enhance the neurotoxicity.
(4) The stoichiometric ratio (1:1), binding site (Tyr10) and dissociation constant (Kd=0.25μmol·-L-1) of NE interacting with Aβwere revealed by electrochemistry and SPR techniques. The physiological significance of Kd was investigated by monitoring the generation of·OH in aerobic solutions containing Cu2+. The results demonstrate that NE inhibits the interaction of Aβ with Cu2+, enhances the generation of-OH. The CD results preliminarily imply that NE may improve the formation of Aβ oligomer.
(1)获得Aβ-Cu2+络合物的解离常数是探讨AD治疗方案的基础之一,但现有文献报道中没有涉及到酸性条件下的Aβ-Cu2+解离常数。本论文采用表面等离子体激元共振(surface plasmon resonance,SPR)技术研究了酸性条件下Ap与Cu2+相互作用的动力学,发现随着溶液环境从中性(pH7.0)到弱酸性(pH4.0), Aβ-Cu2+的解离常数从3.5×10-8mol·L-1增大到8.7×10-3mol·L-1。通过定量检测-OH的产生量,发现酸性环境下Cu2+催化产生·OH的能力增强,毒性增大；随着pH的升高,Aβ结合Cu2+的能力增强,抑制了Cu2+催化产生·OH的反应,降低了其细胞毒性。
(2)溶剂的选择影响Ap-Cu2+解离常数的检测。通常认为Tris是检测Aβ-Cu2+解离常数的理想溶剂。但作为亲核试剂,Tris对Aβ/Cu2+相互作用的影响尚不清楚。本论文采用多种方法系统研究了不同环境条件下Tris对Aβ/Cu2+相互作用的影响。透射电镜和电喷雾电离质谱结果证明酸性条件下可形成Tris-Aβ-Cu2+三元络合物。采用SPR、紫外吸收光谱和电化学技术发现,Tris对Aβ/Cu2+相互作用的影响：Kd增大一个数量级；阻碍Ap与Cu2+之间的电荷迁移,减弱其相应的紫外吸收；Aβ-Cu2+的氧化电位正移。通过定量检测-OH的产生量发现,由于Tris对于Aβ络合Cu2+的反应有竞争作用,使Aβ1-42-Cu2+的解离常数增大,溶液中游离Cu2+增多,所以Tris溶液中-OH的产量增大。中性条件下Tris与Ap无相互作用,不利于三元络合物的生成。
(3)研究Ap与DA的相互作用机理可解释DA在Ap的毒性和AD的发展中所起的作用。采用SPR和电化学技术研究了亲水段Aβ1-16与DA相互作用的化学计量比、作用位点和Kd。结果显示：Aβ1-16与DA相互作用的化学计量比为1：1；DA的酚羟基与Ap的Tyr10结合；Kd为0.30μmpl·L-1。通过定量检测·OH的产生量发现,适当浓度的DA可以释放Aβ-Cu2+中的Cu2+,增大·OH的产生量,增强其细胞毒性。圆二色光谱数据初步说明,Ap与DA的相互作用有可能促进Aβ寡聚体的形成,加剧脑部的神经毒性。
(4)SPR和电化学研究显示NE与Ap的相互作用机制与DA/Aβ的相似：化学计量比为1：1；NE的酚羟基与Ap的Tyr10结合；Kd为0.25μmol·L-1。通过定量检测·OH的产生量发现,适当浓度的NE可以释放A(3-Cu2+中的Cu2+,促进·OH的产生。圆二色光谱数据初步说明,Ap与NE的相互作用可能会促进Ap寡聚体的形成,加剧脑部局部区域的神经毒性。
A(3is the major constitute of senile plaque, a hallmark in the brain of AD victims. It is well-known that Aβ is crucial for the development of AD. The interactions of Aβ with neurotransmitters (Cu DA and NE) may affect the neuron. And the interactions of A(3with Cu2+DA and NE are very important for the neurobiological processes and pathogenesis of AD, therefore, the mechanisms of A(3interacting with Cu2+, DA and NE are investigated to get the kinetic constants, and the roles of A(3interacting with Cu2+, DA and NE in the pathogenesis of AD are discussed preliminarily. Base on the above considerations, the following studies were carried out.
(1) Interactions of Aβ with Cu2+are known to be pH-dependent and believed to play a crucial role in the neurotoxicity of AD. However, there is no reports about the affinity of Aβ-Cu2+under acidic pH. In this study, SPR sensor with immobilized Aβ was used to investigate the formation of Aβ-Cu2+complexes under acidic pH conditions. Dissociation constants (Kd) were calculated and shown to be pH-dependent, ranging from8.7×10-3to3.5×10-8mol·L-1under pH4.0-7.0. The physiological significance of Kd was preliminarily investigated by monitoring the generation of·OH in aerobic solutions containing Aβ-Cu2+and Cu2+. The results imply that acidic conditions could aggravate the oxidative stress in the presence of Cu2+, and the weak affinities of Aβ-Cu2+under acidic pH could further enhance the oxidative damage. However, under mildly acidic pH conditions, the formation of Ap-Cu2+reduced free Cu2+, inhibited the generation of·OH. In biological milieu, Aβ could protect neuron from oxidative stress.
(2) Numerous studies in the recent ten years show a large variation on the dissociation constant of Aβ-Cu2+under different solvent conditions. Among the common buffers, Tris is considered to be the most reliable. However, Tris is rich of nucleophilic groups, so it may have a more diversified role in the interaction of Aβ with Cu2+. Under acidic conditions, a Tris-Aβ-Cu2+ternary complex was identified using ESI-MS and TEM. The results of surface plasmon resonance reveal that the formation of a ternary complex increases the dissociation constant by almost one order of magnitude. Consequently, toxicity assessment indicates that the generation of-OH induced by the Aβ-Cu2+complex is enhanced in the presence of Tris. Increased pH condition disfavors the formation of Tris-Ap-Cu2+complex.
(3) Due to the controversial effects of DA on the toxicity of Aβ and the development of AD, it is necessary to understand the interaction of Aβ with DA. In this study, the stoichiometric ratio (1:1), binding site (Tyr10) and dissociation constant (KA=0.30μmol·L-1) of DA interacting with Aβ1-16were revealed. The physiological significance of Kd was investigated by monitoring the generation of·OH in aerobic solutions containing Cu2+. The results demonstrat that DA inhibits the interaction of Aβ with Cu2+, enhances the generation of-OH. The CD results preliminarily imply that DA may improve the formation of Aβ oligomer, and then enhance the neurotoxicity.
(4) The stoichiometric ratio (1:1), binding site (Tyr10) and dissociation constant (Kd=0.25μmol·-L-1) of NE interacting with Aβwere revealed by electrochemistry and SPR techniques. The physiological significance of Kd was investigated by monitoring the generation of·OH in aerobic solutions containing Cu2+. The results demonstrate that NE inhibits the interaction of Aβ with Cu2+, enhances the generation of-OH. The CD results preliminarily imply that NE may improve the formation of Aβ oligomer.
引文
[1]Stelzmann R A, Norman Schnitzlein H, Reed Murtagh F. An english translation of alzheimer's 1907 paper, "uber eine eigenartige erkankung der hirnrinde" [J]. Clin. Anat.,1995,8(6):429-431.
[2]Mattson M P. Pathways towards and away from Alzheimer's disease [J]. Nature,2004,430(7000):631-639.
[3]Hung Y, Bush A, Cherny R. Copper in the brain and Alzheimer's disease [J]. J. Biol. Inorg. Chem.,2010,15(1):61-76.
[4]Esteban J A. Living with the enemy:A physiological role for the β-amyloid peptide [J]. Trends Neurosci.,2004,27(1):1-3.
[5]Blennow K, de Leon M J, Zetterberg H. Alzheimer's disease [J]. Lancet,2006, 368:387-403.
[6]Mann D M A, Tucker C M, Yates P O. The topographic distribution of senile plaques and neurofibrillary tangles in the brains of non-demented persons of different ages [J]. Neuropath. Appl. Neuro.,1987,13(2):123-139.
[7]Naslund J, Haroutunian V, Mohs R, et al. Correlation between elevated levels of amyloid β-peptide in the brain and cognitive decline [J]. J. Am. Med. Assoc.,2000,283(12):1571-1577.
[8]Goedert M, Spillantini M G. A century of Alzheimer's disease [J]. Science, 2006,314(5800):777-781.
[9]Masters C L, Simms G, Weinman N A, et al. Amyloid plaque core protein in Alzheimer disease and Down syndrome [J]. Proc. Natl. Acad. Sci. USA,1985, 82(12):4245-4249.
[10]Glenner G G, Wong C W. Alzheimer's disease:Initial report of the purification and characterization of a novel cerebrovascular amyloid protein [J]. Biochem. Biophy. Res. Co.,1984,120(3):885-890.
[11]Cherny R A, Legg J T, McLean C A, et al. Aqueous dissolution of Alzheimer's disease Aβ amyloid deposits by biometal depletion [J]. J. Biol. Chem.,1999, 274(33):23223-23228.
[12]Armstrong R A. The molecular biology of senile plaques and neurofibrillary tangles in Alzheimer's disease [J]. Folia Neuropathol.,2009,47(4):289-299.
[13]Grundke-Iqbal I, Iqbal K, Tung Y C, et al. Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology [J]. Proc. Natl. Acad. Sci. USA,1986,83(13):4913-4917.
[14]Buee-Scherer V, Condamines O, Mourton-Gilles C, et al. AD2, a phosphorylation-dependent monoclonal antibody directed against tau proteins found in Alzheimer's disease [J]. Mol. Brain Res.,1996,39(1-2):79-88.
[15]Hardy J, Selkoe D J. The amyloid hypothesis of Alzheimer's disease:progress and problems on the road to therapeutics [J]. Science,2002,297(5580): 353-356.
[16]Iqbal K, Alonso A C, Chen S, et al. Tau pathology in Alzheimer disease and other tauopathies [J]. Biochim. Biophys. Acta,2005,1739(2-3):198-210.
[17]Babic T. The cholinergic hypothesis of Alzheimer's disease:a review of progress [J]. J. Neurol Neurosur. Ps.,1999,67(4):558.
[18]Gibson G E, Huang H M. Oxidative stress in Alzheimer's disease [J]. Neurobiol. Aging,2005,26(5):575-578.
[19]Aisen P S. The potential of anti-inflammatory drugs for the treatment of Alzheimer's disease [J]. Lancet Neurol.,2002,1(5):279-284.
[20]Reddy P H, Beal M F. Are mitochondria critical in the pathogenesis of Alzheimer's disease? [J]. Brain Res. Rev.,2005,49(3):618-632.
[21]Selkoe D J. Alzheimer's disease-genotypes, phenotype, and treatments [J]. Science,1997,275(5300):630-631.
[22]Rauk A. The chemistry of Alzheimer's disease [J]. Chem Soc Rev,2009,38(9): 2698-715.
[23]Tougu V, Tiiman A, Palumaa P. Interactions of Zn(ⅱ) and Cu(ⅱ) ions with Alzheimer's amyloid-β peptide. Metal ion binding, contribution to fibrillization and toxicity [J]. Metallomics,2011,3(3):250-261.
[24]Hensley K, Carney J M, Mattson M P, et al. A model for p-amyloid aggregation and neurotoxicity based on free radical generation by the peptide: relevance to Alzheimer disease [J]. Proc. Natl. Acad. Sci. USA,1994,91(8): 3270-3274.
[25]Goodman Y, Mattson M P. Secreted forms of β-amyloid precursor protein protect hippocampal neurons against amyloid β-peptide-induced oxidative injury [J]. Exp. Neurol.,1994,128(1):1-12.
[26]Behl C, Davis J B, Lesley R, et al. Hydrogen peroxide mediates amyloid β protein toxicity [J]. Cell,1994,77(6):817-827.
[27]Lovell M A, Ehmann W D, Butler S M, et al. Elevated thiobarbituric acid-reactive substances and antioxidant enzyme activity in the brain in Alzheimer's disease [J]. Neurology,1995,45(8):1594-1601.
[28]Smith C D, Carney J M, Starke-Reed P E, et al. Excess brain protein oxidation and enzyme dysfunction in normal aging and in Alzheimer disease [J]. Proc. Natl. Acad. Sci. USA,1991,88(23):10540-10543.
[29]Smith M, Sayre L, Monnier V, et al. Oxidative posttranslational modifications in Alzheimer disease [J]. Mol. Chem. Neuropath.,1996,28(1-3):41-48.
[30]Mecocci P, MacGarvey U, Beal M F. Oxidative damage to mitochondrial DNA is increased in Alzheimer's disease [J]. Ann. Neurol.,1994,36(5):747-751.
[31]Hashimoto M, Rockenstein E, Crews L, et al. Role of protein aggregation in mitochondrial dysfunction and neurodegeneration in Alzheimer's and Parkinson's diseases [J]. Neuromol. Med.,2003,4(1-2):21-35.
[32]Upadhyaya P, Seth V, Ahmad M. Therapy of Alzheimer's disease:An update [J]. Afr. Pharm. Pharmaco.,2010,4(6):408-421.
[33]Dessalew N, Patel D S, Bharatam P V.3D-QSAR and molecular docking studies on pyrazolopyrimidine derivatives as glycogen synthase kinase-3β inhibitors [J]. J. Mol. Graph. Model.,2007,25(6):885-895.
[34]Francis P T, Nordberg A, Arnold S E. A preclinical view of cholinesterase inhibitors in neuroprotection:do they provide more than symptomatic benefits in Alzheimer's disease? [J]. Trends Pharmacol. Sci.,2005,26(2):104-111.
[35]Pendurthi U R, Rao L V M. Suppression of transcription factor Egr-1 by curcumin [J]. Thrombosis Res.,2000,97(4):179-189.
[36]Grasso G. The use of mass spectrometry to study amyloid-β peptides [J]. Mass Spectrom. Rev.,2011,30(3):347-365.
[37]Vassar R, Bennett B D, Babu-Khan S, et al.β-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE [J]. Science,1999,286(5440):735-741.
[38]Kojro E, Fahrenholz F. The non-amyloidogenic pathway:Structure and function of a-secretases Alzheimer's disease [M]. US:Springer,2005: 105-127.
[39]Yokoyama K, Welchons D R. The conjugation of amyloid (3 protein on the gold colloidal nanoparticles' surfaces [J]. Nanotechnology,2007,18(10): 105101(7pp).
[40]Hartley D M, Walsh D M, Ye C P, et al. Protofibrillar intermediates of amyloid β-protein induce acute electrophysiological changes and progressive neurotoxicity in cortical neurons [J]. J. Neurosci.,1999,19(20):8876-8884.
[41]Fezoui Y, Hartley D M, Harper J D, et al. An improved method of preparing the amyloid β-protein for fibrillogenesis and neurotoxicity experiments [J]. Amyloid,2000,7(3):166-178.
[42]Golde T E, Eckman C B, Younkin S G. Biochemical detection of AP isoforms: implications for pathogenesis, diagnosis, and treatment of Alzheimer's disease [J]. BBA-Mol. Basis Dis.,2000,1502(1):172-187.
[43]Roberson E D, Mucke L.100 years and counting:Prospects for defeating Alzheimer's disease [J]. Science,2006,314(5800):781-784.
[44]Rozga M, Kloniecki M, Dadlez M, et al. A direct determination of the dissociation constant for the Cu(II) complex of amyloid P 1-40 peptide [J]. Chem. Res. Toxicol.,2010,23:336-340.
[45]Selkoe D J. Alzheimer's disease:Genes, proteins, and therapy [J]. Physiol. Rev.,2001,81(2):741-766.
[46]Marchesi V T. An alternative interpretation of the amyloid Aβ hypothesis with regard to the pathogenesis of Alzheimer's disease [J]. Proc. Natl. Acad. Sci. USA,2005,102(26):9093-9098.
[47]Hung L W, Ciccotosto G D, Giannakis E, et al. Amyloid-β peptide (Aβ) neurotoxicity is modulated by the rate of peptide aggregation:Aβ dimers and trimers correlate with neurotoxicity [J]. J. Neurosci.,2008,28(46): 11950-11958.
[48]Shankar G M, Li S, Mehta T H, et al. Amyloid-β protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory [J]. Nat. Med.,2008,14(8):837-842.
[49]Kayed R, Pensalfini A, Margol L, et al. Annular protofibrils are a structurally and functionally distinct type of amyloid oligomer [J]. J. Biol. Chem.,2009, 284(7):4230-4237.
[50]Martins I C, Kuperstein I, Wilkinson H, et al. Lipids revert inert Aβ amyloid fibrils to neurotoxic protofibrils that affect learning in mice [J]. EMBO J., 2008,27(1):224-233.
[51]Jiang D, Rauda I, Han S, et al. Aggregation pathways of the amyloid β(1-42) peptide depend on its colloidal stability and ordered P-sheet stacking [J]. Langmuir,2012,28(35):12711-12721.
[52]Rao K S J, Hegde M L, Anitha S, et al. Amyloid β and neuromelanin-Toxic or protective molecules?:The cellular context makes the difference [J]. Prog. Neurobiol.,2006,78(6):364-373.
[53]Varadarajan S, Yatin S, Aksenova M, et al. Review:Alzheimer's amyloid (3-peptide-associated free radical oxidative stress and neurotoxicity [J]. J. Struct. Biol.,2000,130(2-3):184-208.
[54]Yankner B, Dawes L, Fisher S, et al. Neurotoxicity of a fragment of the amyloid precursor associated with Alzheimer's disease [J]. Science,1989, 245(4916):417-420.
[55]Klein W L, Stine Jr W B, Teplow D B. Small assemblies of unmodified amyloid β-protein are the proximate neurotoxin in Alzheimer's disease [J]. Neurobiol. Aging,2004,25(5):569-580.
[56]Gemma C, Mark A S, Xiongwei Z, et al. Alzheimer disease:Evidence for a central pathogenic role of iron-mediated reactive oxygen species [J]. J. Alzheimers Dis.,2004,6(2):165-169.
[57]Hureau C, Faller P. AP-mediated ROS production by Cu ions:Structural insights, mechanisms and relevance to Alzheimer's disease [J]. Biochimie, 2009,91(10):1212-1217.
[58]Gong J, Sawamura N, Zou K, et al. Amyloid β-protein affects cholesterol metabolism in cultured neurons:Implications for pivotal role of cholesterol in the amyloid cascade [J]. J. Neurosci. Res.,2002,70(3):438-446.
[59]Atwood C S, Obrenovich M E, Liu T, et al. Amyloid-β:A chameleon walking in two worlds:A review of the trophic and toxic properties of amyloid-β [J]. Brain Res. Rev.,2003,43(1):1-16.
[60]Faller P, Hureau C. Bioinorganic chemistry of copper and zinc ions coordinated to amyloid-p peptide [J]. Dalton T.,2009,7:1080-1094.
[61]Stadtman E R, Moskovitz J, L. L R. Oxidation of methionine residues of proteins:Biological consequences [J]. Antioxid. Redox Signal.,2003,5:577-582.
[62]Luo Y, Sunderland T, Roth G S, et al. Physiological levels of β-amyloid peptide promote PC 12 cell proliferation [J]. Neurosci. Lett.,1996,217(2-3): 125-128.
[63]Plant L D, Boyle J P, Smith I F, et al. The production of amyloid β peptide is a critical requirement for the viability of central neurons [J]. J. Neurosci.,2003, 23(13):5531-5535.
[64]Gaggelli E, Kozlowski H, Valensin D, et al. Copper homeostasis and neurodegenerative disorders (Alzheimer's, prion, and Parkinson's diseases and amyotrophic lateral sclerosis) [J]. Chem. Rev.,2006,106(6):1995-2044.
[65]Adlard P A, Bush A I. Metals and Alzheimer's disease [J]. J. Alzheimers Dis., 2006,10(2):145-163.
[66]Zatta P, Drago D, Bolognin S, et al. Alzheimer's disease, metal ions and metal homeostatic therapy [J]. Trends Pharmacol. Sci.,2009,30(7):346-355.
[67]Hutchinson R W, Cox A G, McLeod C W, et al. Imaging and spatial distribution of β-amyloid peptide and metal ions in Alzheimer's plaques by laser ablation-inductively coupled plasma-mass spectrometry [J]. Anal. Biochem.,2005,346(2):225-233.
[68]Curtain C C, Ali F, Volitakis I, et al. Alzheimer's disease amyloid-β binds copper and zinc to generate an allosterically ordered membrane-penetrating structure containing superoxide dismutase-like subunits [J]. J. Biol. Chem., 2001,276(23):20466-20473.
[69]Atwood C S, Moir R D, Huang X, et al. Dramatic aggregation of Alzheimer AP by Cu(Ⅱ) is induced by conditions representing physiological acidosis [J]. J. Biol. Chem.,1998,273(21):12817-12826.
[70]Sarell C J, Wilkinson S R, Viles J H. Substoichiometric levels of Cu2+ ions accelerate the kinetics of fiber formation and promote cell toxicity of amyloid-β from Alzheimer disease [J]. J. Biol. Chem.,2010,285(53): 41533-41540.
[71]Bush A I, Tanzi R E. Therapeutics for Alzheimer's disease based on the metal hypothesis [J]. Neurotherapeutics,2008,5(3):421-432.
[72]Syme C D, Nadal R C, Rigby S E J, et al. Copper binding to the amyloid-P (Aβ) peptide associated with Alzheimer's disease [J]. J. Biol. Chem.,2004, 279(18):18169-18177.
[73]Guilloreau L, Damian L, Coppel Y, et al. Structural and thermodynamical properties of Cull amyloid β 16/28 complexes associated with Alzheimer's disease [J]. J. Biol. Inorg. Chem.,2006,11(8):1024-1038.
[74]Minicozzi V, Stellato F, Comai M, et al. Identifying the minimal copper-and zinc-binding site sequence in amyloid-β peptides [J]. J. Biol. Chem.,2008, 283(16):10784-10792.
[75]Hureau C, Coppel Y, Dorlet P, et al. Deprotonation of the Aspl-Ala2 peptide bond induces modification of the dynamic copper(Ⅱ) environment in the amyloid-β peptide near physiological pH [J]. Angew. Chem. Int. Ed.,2009, 48(50):9522-9525.
[76]Drew S C, Masters C L, Barnham K J. Alanine-2 carbonyl is an oxygen ligand in Cu2+ coordination of Alzheimer's disease amyloid-β peptide-relevance to N-terminally truncated forms [J]. J. Am. Chem. Soc.,2009,131(25): 8760-8761.
[77]Shin B, Saxena S. Direct evidence that all three histidine residues coordinate to Cu(Ⅱ) in amyloid-β1-16 [J]. Biochemistry,2008,47(35):9117-9123.
[78]Sarell C J, Syme C D, Rigby S E J, et al. Copper(Ⅱ) binding to amyloid-(3 fibrils of Alzheimer's disease reveals a picomolar affinity:stoichiometry and coordination geometry are independent of Aβ oligomeric form [J]. Biochemistry,2009,48(20):4388-4402.
[79]Dorlet P, Gambarelli S, Faller P, et al. Pulse EPR spectroscopy reveals the coordination sphere of copper(Ⅱ) ions in the 1-16 amyloid-βpeptide:A key role of the first two N-terminus residues [J]. Angewandte Chemie,2009, 121(49):9437-9440.
[80]Atwood C S, Scarpa R C, Huang X, et al. Characterization of copper interactions with Alzheimer amyloid β peptides:Identification of an attomolar-affinity copper binding site on amyloid β1-42 [J]. J. Neurochem., 2000,75:1219-1233.
[81]Garzon-Rodriguez W, Yatsimirsky A K, Glabe C G. Binding of Zn(Ⅱ), Cu(Ⅱ), and Fe(Ⅱ) ions to Alzheimer's Aβ peptide studied by fluorescence [J]. Bioorg. Med. Chem. Lett.,1999,9(15):2243-2248.
[82]Zawisza I, Rozga M, Bal W. Affinity of copper and zinc ions to proteins and peptides related to neurodegenerative conditions (Aβ, APP, a-synuclein, PrP) [J]. Coordin Chem. Rev.,2012,256(19-20):2297-2307.
[83]Rozga M, Bal W. The Cu(Ⅱ)/Aβ/human serum albumin model of control mechanism for copper-related amyloid neurotoxicity [J]. Chem. Res. Toxicol., 2010,23(2):298-308.
[84]Tougu V, Karafin A, Palumaa P. Binding of zinc(Ⅱ) and copper(Ⅱ) to the full-length Alzheimer's amyloid-p peptide [J]. J. Neurochem.,2008,104(5): 1249-1259.
[85]Rozga M, Protas A M, Jablonowska A, et al. The Cu(Ⅱ) complex of Aβ40 peptide in ammonium acetate solutions. Evidence for ternary species formation [J]. Chem. Commun.,2009,11:1374-1376.
[86]Xiao Z, Wedd A G. The challenges of determining metal-protein affinities [J]. Nat. Prod. Rep.,2010,27(5):768-789.
[87]Hatcher L Q, Hong L, Bush W D, et al. Quantification of the binding constant of copper(Ⅱ) to the amyloid-β peptide [J]. J. Phys. Chem. B,2008,112(27): 8160-8164.
[88]Kowalik-Jankowska T, Ruta M, Wisniewska K, et al. Coordination abilities of the 1-16 and 1-28 fragments of β-amyloid peptide towards copper(Ⅱ) ions:a combined potentiometric and spectroscopic study [J]. J. Inorg. Biochem.,2003, 95(4):270-282.
[89]Ma Q, Hu J, Wu W H, et al. Characterization of copper binding to the peptide amyloid-β(1-16) associated with Alzheimer's disease [J]. Biopolymers,2006, 83(1):20-31.
[90]Hong L, Bush W D, Hatcher L Q, et al. Determining thermodynamic parameters from isothermal calorimetric isotherms of the binding of macromolecules to metal cations originally chelated by a weak ligand [J]. J. Phys. Chem. B,2007,112(2):604-611.
[91]Maiti N C, Jiang D L, Wain A J, et al. Mechanistic studies of Cu(Ⅱ) binding to amyloid-β peptides and the fluorescence and redox behaviors of the resulting complexes [J]. J. Phys. Chem. B,2008,112(28):8406-8411.
[92]Banci L, Bertini I, Ciofi-Baffoni S, et al. Affinity gradients drive copper to cellular destinations [J]. Nature,2010,465(7298):645-648.
[93]Jiang D, Li X, Williams R, et al. Ternary complexes of iron, amyloid-β, and nitrilotriacetic acid:binding affinities, redox properties, and relevance to iron-induced oxidative stress in Alzheimer's disease [J]. Biochemistry,2009, 48(33):7939-7947.
[94]Gu Z, Zhong P, Yan Z. Activation of muscarinic receptors inhibits p-amyloid peptide-induced signaling in cortical slices [J]. J. Biol. Chem.,2003,278(19): 17546-17556.
[95]Mitchell R A, Herrmann N, Lanctot K L. The role of dopamine in symptoms and treatment of apathy in Alzheimer's disease [J]. CNS Neurosci. Ther.,2011, 17(5):411-427.
[96]Marien M R, Colpaert F C, Rosenquist A C. Noradrenergic mechanisms in neurodegenerative diseases:a theory [J]. Brain Res. Rev.,2004,45(1):38-78.
[97]Perez-Garcia G S, Meneses A. Effects of the potential 5-HT7 receptor agonist AS 19 in an autoshaping learning task [J]. Behav. Brain Res.,2005,163(1): 136-140.
[98]Andorn A C, Pappolla M A. Catecholamines inhibit lipid peroxidation in young, aged, and Alzheimer's disease brain [J]. Free Radical Biol. Med.,2001, 31(3):315-320.
[99]Opazo C. Metalloenzyme-like activity of Alzheimer's disease P-amyloid. Cu-dependent catalytic conversion of dopamine, cholesterol, and biological reducing agents to neurotoxic H2O2 [J]. J. Biol. Chem.,2002,277(43): 40302-40308.
[100]Huong V T, Shimanouchi T, Shimauchi N, et al. Catechol derivatives inhibit the fibril formation of amyloid-β peptides [J]. J. Biosci. Bioeng.,2010,109(6): 629-634.
[101]German D C, Manaye K F, White C L, et al. Disease-specific patterns of locus coeruleus cell loss [J]. Ann. Neurol.,1992,32(5):667-676.
[102]Heinonen E H, Savijarvi M, Kotila M. Effects of monoamine oxidase inhibition by selegline on concentration of noradrenaline and monoamine metabolites in CSF of patients with Alzheimer's disease [J]. J. Neuroal. Transm. Park. Dis. Dement. Sect.,1993,5(3):193-202.
[103]Martignoni E, Bono G, Blandini F. Monoamines and related metabolite levels in the cerebrospinal fluid of patients with dementia of Alzheimer type: Influence of treatment with L-depreny [J]. J. Neuroal. Transm. Park. Dis. Dement. Sect.,1991,3(1):15-25.
[104]Sakai N, Sasa M, Ishihara K. Effects of L-threo-DOPS, a noradrenaline precursor, on the long-term potentiation in the rat hippocampal mossy fiber-CA3 region [J]. Brain Res.,1991,20(2):267-273.
[105]Missnnier P, Ragot R, Derouesn C. Automatic attentional shifts induced by a noradrenerg ic drug in Alzheimer's disease:evidence from evoked potentials [J]. Int. J. Psychophysiol.,1999,33(3):243-251.
[106]Rauk A. The chemistry of Alzheimer's disease [J]. Chem. Soc. Rev.,2009, 38(9):2698-715.
[107]King M E, Kan H M, Baas P W, et al. Tau-dependent microtubule disassembly initiated by prefibrillar β-amyloid [J]. J. Cell Biol.,2006,175(4):541-546.
[108]Cedazo-Minguez A, Popescu B O, Blanco-Millan J M, et al. Apolipoprotein E and β-amyloid (1-42) regulation of glycogen synthase kinase-3β [J]. J. Neurochem.,2003,87(5):1152-1164.
[109]Sadowski M J, Pankiewicz J, Scholtzova H, et al. Blocking the apolipoprotein E/amyloid-β interaction as a potential therapeutic approach for Alzheimer's disease [J]. Proc. Natl. Acad. Sci. USA,2006,103(49):18787-18792.
[110]Hartmann T, Kuchenbecker J, Grimm M O W. Alzheimer's disease:the lipid connection [J]. J. Neurochem.,2007,103:159-170.
[111]Yao Z, Papadopoulos V. Function of β-amyloid in cholesterol transport:a lead to neurotoxicity [J]. FASEB J.,2002,16(12):1677-1679.
[112]Puglielli L, Friedlich A L, Setchell K D R, et al. Alzheimer disease β-amyloid activity mimics cholesterol oxidase [J]. J. Clin. Invest.,2005,115(9): 2556-2563.
[113]Shimanouchi T, Tasaki M, Vu H T, et al. Aβ/Cu-catalyzed oxidation of cholesterol in 1,2-dipalmitoyl phosphatidylcholine liposome membrane [J]. J. Biosci. Bioeng.,2010,109(2):145-148.
[114]Milton N G. Amyloid-β binds catalase with high affinity and inhibits hydrogen peroxide breakdown [J]. Biochem. J,1999,344:293-296.
[115]赵晓君,陈焕文,宋大千等,表面等离子体子共振传感器1：基本原理[J],分析仪器,2000,4：1-8。
[116]http://www.biosensingusa.com/BI-3000.html
[117]Lovell M A, Robertson J D, Teesdale W J, et al. Copper, iron and zinc in Alzheimer's disease senile plaques [J]. J. Neurol. Sci.,1998,158(1):47-52.
[118]Pecci L, Montefoschi G, Cavallini D. Some new details of the copper-hydrogen peroxide interaction. [J]. Biochem. Biophys. Res. Co.,1997, 235:264-267.
[119]Atwood C S, Perry G, Zeng H, et al. Copper mediates dityrosine cross-linking of Alzheimer's amyloid-β[J]. Biochemistry,2003,43(2):560-568.
[120]Dikalov S I, Vitek M P, Mason R P. Cupric-amyloid β peptide complex stimulates oxidation of ascorbate and generation of hydroxyl radical [J]. Free Radical Biol. Med.,2004,36(3):340-347.
[121]Guilloreau L, Combalbert S, Sournia-Saquet A, et al. Redox chemistry of copper-amyloid-β:The generation of hydroxyl radical in the presence of ascorbate is linked to redox-potentials and aggregation state [J]. ChemBioChem,2007,8(11):1317-1325.
[122]Pithadia A S, Lim M H. Metal-associated amyloid-β species in Alzheimer's disease [J]. Curr. Opin. Chem. Biol.,2012,16(1-2):67-73.
[123]Yoshiike Y, Tanemura K, Murayama O, et al. New insights on how metals disrupt amyloid β-aggregation and their effects on amyloid-p cytotoxicity [J]. J. Biol. Chem.,2001,276(34):32293-32299.
[124]Miura T, Suzuki K, Kohata N, et al. Metal binding modes of Alzheimer's amyloid β-peptide in insoluble aggregates and soluble complexes [J]. Biochemistry,2000,39(23):7024-7031.
[125]Suzuki K, Miura T, Takeuchi H. Inhibitory effect of Copper(Ⅱ) on Zinc(Ⅱ)-induced aggregation of amyloid β-peptide [J]. Biochem. Biophys. Res. Co.,2001,285(4):991-996.
[126]Ali-Torres J, Marechal J-D, Rodriguez-Santiago L, et al. Three dimensional models of Cu2+-Aβ(1-16) complexes from computational approaches [J]. J. Am. Chem. Soc.,2011,133(38):15008-15014.
[127]Grant S A, Bettencourt K, Krulevitch P, et al. In vitro and in vivo measurements of fiber optic and electrochemical sensors to monitor brain tissue pH [J]. Sensor. Actuator. B:Chemical,2001,72(2):174-179.
[128]Su Y, Chang P T. Acidic pH promotes the formation of toxic fibrils from β-amyloid peptide [J]. Brain Res.,2001,893(1-2):287-291.
[129]Harguindey S, Reshkin S J, Orive G, et al. Growth and trophic factors, pH and the Na+/H+ exchanger in Alzheimer's disease, other neurodegenerative diseases and cancer:New therapeutic possibilities and potential dangers [J]. Curr. Alzheimer Res.,2007,4(1):53-65.
[130]Jiang D, Men L, Wang J, et al. Redox reactions of copper complexes formed with different β-amyloid peptides and their neuropathalogical relevance [J]. Biochemistry,2007,46(32):9270-9282.
[131]Xin Y, Gao Y, Guo J, et al. Real-time detection of Cu2+ sequestration and release by immobilized apo-metallothioneins using SECM combined with SPR [J]. Biosens. Bioelectron.,2008,24(3):369-375.
[132]Myszka D G. Kinetic analysis of macromolecular interactions using surface plasmon resonance biosensors [J]. Curr. Opin. Biotech.,1997,8(1):50-57.
[133]Bin Y, Chen S, Xiang J. pH-dependent kinetics of copper ions binding to amyloid-β peptide [J]. J. Inorg. Biochem.,2013,119:21-27.
[134]O'shannessy D J, Brighamburke M, Soneson K K, et al. Determination of rate and equilibrium binding constants for macromolecular interactions using surface plasmon resonance:use of nonlinear least squares analysis methods [J]. Anal. Biochem.,1993,212(2):457-468.
[135]Wegner G J, Wark A W, Lee H J, et al. Real-time surface plasmon resonance imaging measurements for the multiplexed determination of protein adsorption/desorption kinetics and surface enzymatic reactions on peptide microarrays [J]. Anal. Chem.,2004,76(19):5677-5684.
[136]Manevich Y, Held K D, Biaglow J E. Coumarin-3-carboxylic acid as a detector for hydroxyl radicals generated chemically and by gamma radiation [J]. Radiat. Res.,1997,148(6):580-591.
[137]Nadal R C, Rigby S E J, Viles J H. Amyloid β-Cu2+ complexes in both monomeric and fibrillar forms do not generate H2O2 catalytically but quench hydroxyl radicals [J]. Biochemistry,2008,47(44):11653-11664.
[138]Huang E, Zhou F, Deng L. Studies of surface coverage and orientation of DNA molecules immobilized onto preformed alkanethiol self-assembled monolayers [J]. Langmuir,2000,16(7):3272-3280.
[139]Su X, O'Shea S J. Determination of monoenzyme-and bienzyme-stimulated precipitation by a cuvette-based surface plasmon resonance instrument [J]. Anal. Biochem.,2001,299(2):241-246.
[140]Thakur G, Micic M, Leblanc R M. Surface chemistry and spectroscopy of amyloid β (1-42) mixed with and conjugated to quantum dots langmuir monolayer [J]. J. Phys. Chem. C,2010,114(35):15084-15093.
[141]Martell A E, Smith R M. NIST Standard Reference Database 46.2004, version 8.0.
[142]Chen W T, Liao Y H, Yu H M, et al. Distinct effects of Zn2+, Cu2+, Fe3+, and Al3+ on amyloid-P stability, oligomerization, and aggregation:amyloid-β destabilization promotes annular protofibril formation [J]. J. Biol. Chem., 2011,286(11):9646-9656.
[143]Smith D G, Cappai R, Barnham K J. The redox chemistry of the Alzheimer's disease amyloid β peptide [J]. Biochim. Biophys. Acta.,2007,1768(8): 1976-1990.
[144]Rozga M, Sokolowska M, Protas A, et al. Human serum albumin coordinates Cu(Ⅱ) at its N-terminal binding site with 1 pM affinity [J]. J. Biol. Inorg. Chem.,2007,12(6):913-918.
[145]Jiang D, Li X, Gargey Y, et al. Reaction rates and mechanism of the ascorbic acid oxidation by molecular oxygen facilitated by Cu(Ⅱ)-containing amyloid-β complexes and aggregates. [J]. J. Phys. Chem. B,2010,114(14):4896-4903.
[146]Kowalewski T, Holtzman D M. In situ atomic force microscopy study of Alzheimer's P-amyloid peptide on different substrates:New insights into mechanism of p-sheet formation [J]. Proc. Natl. Acad. Sci. USA,1999,96(7): 3688-3693.
[147]Smith D P, Ciccotosto G D, Tew D J, et al. Concentration dependent Cu2+ induced aggregation and dityrosine formation of the Alzheimer's disease amyloid-β peptide [J]. Biochemistry,2007,46(10):2881-2891.
[148]Manevich Y, Held K D, Biaglow J E. Coumarin-3-carboxylic acid as a detector for hydroxyl radicals generated chemically and by gamma radiation [J]. Radi. Res.,1997,148(6):580-591.
[149]Ciccotosto G D, Tew D J, Fodero-Tavoletti M T, et al. Concentration dependent Cu(Ⅱ) induced aggregation and dityrosine formation of the Alzheimer's disease Amyloid-β peptide [J]. Biochemistry,2007,46(10): 2881-2891.
[150]Nakamura M, Shishido N, Nunomura A, et al. Three histidine residues of amyloid-β peptide control the redox activity of copper and iron [J]. Biochemistry,2007,46(44):12737-12743.
[151]Anwar Z M, Azab H A. Ternary complexes in solution, comparison of the coordination tendency of some biologically important zwitterionic buffers toward the binary complexes of some transition metal ions and some amino acids [J]. J. Chem. Eng. Data,1999,44(6):1151-1157.
[152]Shin B, Saxena S. Substantial contribution of the two imidazole rings of the His13-His14 dyad to Cu(Ⅱ) binding in amyloid-β(1-16) at physiological pH and its significance [J]. J. Phys. Chem. A,2011,115(34):9590-9602.
[153]Righetti P G, Magnusdottir S, Gelfi C, et al. Behaviour of inorganic and organic cations in the Debye-Hiickel layer of DNA [J]. J. Chromatogr. A, 2001,920(1-2):309-316.
[154]Sun M, Chen J, Liu X H, et al. Molecular interaction modeling of Ser-His dipeptide and buffers [J]. J. Mol. Struc. (Theochem),2004,668(1):47-49.
[155]Quan L, Wei D, Jiang X, et al. Resurveying the Tris buffer solution:The specific interaction between tris(hydroxymethyl)aminomethane and lysozyme [J]. Anal. Biochem.,2008,378(2):144-150.
[156]Taha M, Lee M. Interactions of TRIS tris(hydroxymethyl)aminomethane and related buffers with peptide backbone:Thermodynamic characterization [J]. Phys. Chem. Chem. Phys.,2010,12(39):12840-12850.
[157]Wang Q, Shah N, Zhao J, et al. Structural, morphological, and kinetic studies of β-amyloid peptide aggregation on self-assembled monolayers [J]. Phys. Chem. Chem. Phys.,2011,13(33):15200-15210.
[158]Bin Y, Gao Y, Xiang J, et al. Immobilization of metallothionein on highly oriented pyrolytic graphite for biosensor design [J]. Surf. Interface Anal.,2009, 41:834-838.
[159]Shakked Z, Viswamitra M A, Kennard O. Interactions of tris buffer with nucleotides:The crystal structure of tris(hydroxymethyl)methylammonium adenosine 5'-diphosphate dihydrate [J]. Biochemistry,1980,19(12): 2567-2571.
[160]Compagnini A, Cunsolo V, Foti S, et al. Improved accuracy in the matrix-assisted laser desorption/ionization-mass spectrometry determination of the molecular mass of cyanogen bromide fragments of proteins by post-cleavage reaction with tris(hydroxymethyl)aminomethane [J]. Proteomics, 2001,1(8):967-974.
[161]Burcham P C, Fontaine F R, Petersen D R, et al. Reactivity with tris(hydroxymethyl)aminomethane confounds immunodetection of acrolein-adducted proteins [J]. Chem. Res. Toxicol.,2003,16(10):1196-1201.
[162]Williams D E, Reisfeld R A. Disc electrophoresis in polyacrylamide gels: Extension to new conditions of pH and buffer [J]. Ann. NY Acad. Sci.,1964, 121(2):373-381.
[163]Reinikainen K J, Soininen H, Riekkinen P J. Neurotransmitter changes in alzheimer's disease:Implications to diagnostics and therapy [J]. J. Neurosci. Res.,1990,27(4):576-586.
[164]Selkoe D J. Alzheimer's disease is a synaptic failure [J]. Science,2002, 298(5594):789-791.
[165]Chimon S, Shaibat M A, Jones C R, et al. Evidence of fibril-like β-sheet structures in a neurotoxic amyloid intermediate of Alzheimer's β-amyloid [J]. Nat. Struct. Mol. Biol.,2007,14(12):1157-1164.
[166]Kayed R, Head E, Thompson J L, et al. Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis [J]. Science,2003, 300(5618):486-489.
[167]Deshpande A, Mina E, Glabe C, et al. Different conformations of amyloid β induce neurotoxicity by distinct mechanisms in human cortical neurons [J]. J. Neurosci.,2006,26(22):6011-6018.
[168]Guzman-Ramos K, Moreno-Castilla P, Castro-Cruz M, et al. Restoration of dopamine release deficits during object recognition memory acquisition attenuates cognitive impairment in a triple transgenic mice model of Alzheimer's disease [J]. Learn. Memory,2012,19(10):453-460.
[169]Li J, Zhu M, B. M-B A, et al. Dopamine and L-dopa disaggregate amyloid fibrils:implications for Parkinson's and Alzheimer's disease [J]. FASEB J. 2004,18:962-964.
[170]Fu W, Luo H, Parthasarathy S, et al. Catecholamines potentiate amyloid (3-peptide neurotoxicity:Involvement of oxidative stress, mitochondrial dysfunction, and perturbed calcium homeostasis [J]. Neurobiol. Dis.,1998, 5(4):229-243.
[171]Guzman-Ramos K, Moreno-Castilla P, Castro-Cruz M, et al. Restoration of dopamine release deficits during object recognition memory acquisition attenuates cognitive impairment in a triple transgenic mice model of Alzheimer's disease [J]. Learn. Memory,2012,19(10):453-460.
[172]Di Giovanni S, Eleuteri S, Paleologou K E, et al. Entacapone and tolcapone, two catechol O-methyltransferase inhibitors, block fibril formation of α-synuclein and β-amyloid and protect against amyloid-induced toxicity [J]. J. Biol. Chem.,2010,285(20):14941-14954.
[173]Liu J, Mori A. Monoamine metabolism provides an antioxidant defense in the brain against oxidant-and free radical-induced damage [J]. Arch. Biochem. Biophys.,1993,302(1):118-127.
[174]Wen X, Jia Y, Liu Z. Micellar effects on the electrochemistry of dopamine and its selective detection in the presence of ascorbic acid [J]. Talanta,1999,50(5): 1027-1033.
[175]Michel P P, Hefti F. Toxicity of 6-hydroxydopamine and dopamine for dopaminergic neurons in culture [J]. J. Neurosci. Res.,1990,26(4):428-435.
[176]De Felice F G, Houzel J C, Garcia-Abreu J, et al. Inhibition of Alzheimer's disease β-amyloid aggregation, neurotoxicity, and in vivo deposition by nitrophenols:implications for Alzheimer's therapy [J]. FASEB J.,2001,15(7): 1297-1299.
[177]Foote S L, Bloom F E, Aston-Jones G. Nucleus locus ceruleus:new evidence of anatomical and physiological specificity [J]. Physiol. Rev.,1983,63(3): 844-914.
[178]Kong Y, Ruan L, Qian L, et al. Norepinephrine promotes microglia to uptake and degrade amyloid β peptide through upregulation of mouse formyl peptide receptor 2 and induction of insulin-degrading enzyme [J]. J. Neurosci.,2010, 30(35):11848-11857.
[2]Mattson M P. Pathways towards and away from Alzheimer's disease [J]. Nature,2004,430(7000):631-639.
[3]Hung Y, Bush A, Cherny R. Copper in the brain and Alzheimer's disease [J]. J. Biol. Inorg. Chem.,2010,15(1):61-76.
[4]Esteban J A. Living with the enemy:A physiological role for the β-amyloid peptide [J]. Trends Neurosci.,2004,27(1):1-3.
[5]Blennow K, de Leon M J, Zetterberg H. Alzheimer's disease [J]. Lancet,2006, 368:387-403.
[6]Mann D M A, Tucker C M, Yates P O. The topographic distribution of senile plaques and neurofibrillary tangles in the brains of non-demented persons of different ages [J]. Neuropath. Appl. Neuro.,1987,13(2):123-139.
[7]Naslund J, Haroutunian V, Mohs R, et al. Correlation between elevated levels of amyloid β-peptide in the brain and cognitive decline [J]. J. Am. Med. Assoc.,2000,283(12):1571-1577.
[8]Goedert M, Spillantini M G. A century of Alzheimer's disease [J]. Science, 2006,314(5800):777-781.
[9]Masters C L, Simms G, Weinman N A, et al. Amyloid plaque core protein in Alzheimer disease and Down syndrome [J]. Proc. Natl. Acad. Sci. USA,1985, 82(12):4245-4249.
[10]Glenner G G, Wong C W. Alzheimer's disease:Initial report of the purification and characterization of a novel cerebrovascular amyloid protein [J]. Biochem. Biophy. Res. Co.,1984,120(3):885-890.
[11]Cherny R A, Legg J T, McLean C A, et al. Aqueous dissolution of Alzheimer's disease Aβ amyloid deposits by biometal depletion [J]. J. Biol. Chem.,1999, 274(33):23223-23228.
[12]Armstrong R A. The molecular biology of senile plaques and neurofibrillary tangles in Alzheimer's disease [J]. Folia Neuropathol.,2009,47(4):289-299.
[13]Grundke-Iqbal I, Iqbal K, Tung Y C, et al. Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology [J]. Proc. Natl. Acad. Sci. USA,1986,83(13):4913-4917.
[14]Buee-Scherer V, Condamines O, Mourton-Gilles C, et al. AD2, a phosphorylation-dependent monoclonal antibody directed against tau proteins found in Alzheimer's disease [J]. Mol. Brain Res.,1996,39(1-2):79-88.
[15]Hardy J, Selkoe D J. The amyloid hypothesis of Alzheimer's disease:progress and problems on the road to therapeutics [J]. Science,2002,297(5580): 353-356.
[16]Iqbal K, Alonso A C, Chen S, et al. Tau pathology in Alzheimer disease and other tauopathies [J]. Biochim. Biophys. Acta,2005,1739(2-3):198-210.
[17]Babic T. The cholinergic hypothesis of Alzheimer's disease:a review of progress [J]. J. Neurol Neurosur. Ps.,1999,67(4):558.
[18]Gibson G E, Huang H M. Oxidative stress in Alzheimer's disease [J]. Neurobiol. Aging,2005,26(5):575-578.
[19]Aisen P S. The potential of anti-inflammatory drugs for the treatment of Alzheimer's disease [J]. Lancet Neurol.,2002,1(5):279-284.
[20]Reddy P H, Beal M F. Are mitochondria critical in the pathogenesis of Alzheimer's disease? [J]. Brain Res. Rev.,2005,49(3):618-632.
[21]Selkoe D J. Alzheimer's disease-genotypes, phenotype, and treatments [J]. Science,1997,275(5300):630-631.
[22]Rauk A. The chemistry of Alzheimer's disease [J]. Chem Soc Rev,2009,38(9): 2698-715.
[23]Tougu V, Tiiman A, Palumaa P. Interactions of Zn(ⅱ) and Cu(ⅱ) ions with Alzheimer's amyloid-β peptide. Metal ion binding, contribution to fibrillization and toxicity [J]. Metallomics,2011,3(3):250-261.
[24]Hensley K, Carney J M, Mattson M P, et al. A model for p-amyloid aggregation and neurotoxicity based on free radical generation by the peptide: relevance to Alzheimer disease [J]. Proc. Natl. Acad. Sci. USA,1994,91(8): 3270-3274.
[25]Goodman Y, Mattson M P. Secreted forms of β-amyloid precursor protein protect hippocampal neurons against amyloid β-peptide-induced oxidative injury [J]. Exp. Neurol.,1994,128(1):1-12.
[26]Behl C, Davis J B, Lesley R, et al. Hydrogen peroxide mediates amyloid β protein toxicity [J]. Cell,1994,77(6):817-827.
[27]Lovell M A, Ehmann W D, Butler S M, et al. Elevated thiobarbituric acid-reactive substances and antioxidant enzyme activity in the brain in Alzheimer's disease [J]. Neurology,1995,45(8):1594-1601.
[28]Smith C D, Carney J M, Starke-Reed P E, et al. Excess brain protein oxidation and enzyme dysfunction in normal aging and in Alzheimer disease [J]. Proc. Natl. Acad. Sci. USA,1991,88(23):10540-10543.
[29]Smith M, Sayre L, Monnier V, et al. Oxidative posttranslational modifications in Alzheimer disease [J]. Mol. Chem. Neuropath.,1996,28(1-3):41-48.
[30]Mecocci P, MacGarvey U, Beal M F. Oxidative damage to mitochondrial DNA is increased in Alzheimer's disease [J]. Ann. Neurol.,1994,36(5):747-751.
[31]Hashimoto M, Rockenstein E, Crews L, et al. Role of protein aggregation in mitochondrial dysfunction and neurodegeneration in Alzheimer's and Parkinson's diseases [J]. Neuromol. Med.,2003,4(1-2):21-35.
[32]Upadhyaya P, Seth V, Ahmad M. Therapy of Alzheimer's disease:An update [J]. Afr. Pharm. Pharmaco.,2010,4(6):408-421.
[33]Dessalew N, Patel D S, Bharatam P V.3D-QSAR and molecular docking studies on pyrazolopyrimidine derivatives as glycogen synthase kinase-3β inhibitors [J]. J. Mol. Graph. Model.,2007,25(6):885-895.
[34]Francis P T, Nordberg A, Arnold S E. A preclinical view of cholinesterase inhibitors in neuroprotection:do they provide more than symptomatic benefits in Alzheimer's disease? [J]. Trends Pharmacol. Sci.,2005,26(2):104-111.
[35]Pendurthi U R, Rao L V M. Suppression of transcription factor Egr-1 by curcumin [J]. Thrombosis Res.,2000,97(4):179-189.
[36]Grasso G. The use of mass spectrometry to study amyloid-β peptides [J]. Mass Spectrom. Rev.,2011,30(3):347-365.
[37]Vassar R, Bennett B D, Babu-Khan S, et al.β-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE [J]. Science,1999,286(5440):735-741.
[38]Kojro E, Fahrenholz F. The non-amyloidogenic pathway:Structure and function of a-secretases Alzheimer's disease [M]. US:Springer,2005: 105-127.
[39]Yokoyama K, Welchons D R. The conjugation of amyloid (3 protein on the gold colloidal nanoparticles' surfaces [J]. Nanotechnology,2007,18(10): 105101(7pp).
[40]Hartley D M, Walsh D M, Ye C P, et al. Protofibrillar intermediates of amyloid β-protein induce acute electrophysiological changes and progressive neurotoxicity in cortical neurons [J]. J. Neurosci.,1999,19(20):8876-8884.
[41]Fezoui Y, Hartley D M, Harper J D, et al. An improved method of preparing the amyloid β-protein for fibrillogenesis and neurotoxicity experiments [J]. Amyloid,2000,7(3):166-178.
[42]Golde T E, Eckman C B, Younkin S G. Biochemical detection of AP isoforms: implications for pathogenesis, diagnosis, and treatment of Alzheimer's disease [J]. BBA-Mol. Basis Dis.,2000,1502(1):172-187.
[43]Roberson E D, Mucke L.100 years and counting:Prospects for defeating Alzheimer's disease [J]. Science,2006,314(5800):781-784.
[44]Rozga M, Kloniecki M, Dadlez M, et al. A direct determination of the dissociation constant for the Cu(II) complex of amyloid P 1-40 peptide [J]. Chem. Res. Toxicol.,2010,23:336-340.
[45]Selkoe D J. Alzheimer's disease:Genes, proteins, and therapy [J]. Physiol. Rev.,2001,81(2):741-766.
[46]Marchesi V T. An alternative interpretation of the amyloid Aβ hypothesis with regard to the pathogenesis of Alzheimer's disease [J]. Proc. Natl. Acad. Sci. USA,2005,102(26):9093-9098.
[47]Hung L W, Ciccotosto G D, Giannakis E, et al. Amyloid-β peptide (Aβ) neurotoxicity is modulated by the rate of peptide aggregation:Aβ dimers and trimers correlate with neurotoxicity [J]. J. Neurosci.,2008,28(46): 11950-11958.
[48]Shankar G M, Li S, Mehta T H, et al. Amyloid-β protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory [J]. Nat. Med.,2008,14(8):837-842.
[49]Kayed R, Pensalfini A, Margol L, et al. Annular protofibrils are a structurally and functionally distinct type of amyloid oligomer [J]. J. Biol. Chem.,2009, 284(7):4230-4237.
[50]Martins I C, Kuperstein I, Wilkinson H, et al. Lipids revert inert Aβ amyloid fibrils to neurotoxic protofibrils that affect learning in mice [J]. EMBO J., 2008,27(1):224-233.
[51]Jiang D, Rauda I, Han S, et al. Aggregation pathways of the amyloid β(1-42) peptide depend on its colloidal stability and ordered P-sheet stacking [J]. Langmuir,2012,28(35):12711-12721.
[52]Rao K S J, Hegde M L, Anitha S, et al. Amyloid β and neuromelanin-Toxic or protective molecules?:The cellular context makes the difference [J]. Prog. Neurobiol.,2006,78(6):364-373.
[53]Varadarajan S, Yatin S, Aksenova M, et al. Review:Alzheimer's amyloid (3-peptide-associated free radical oxidative stress and neurotoxicity [J]. J. Struct. Biol.,2000,130(2-3):184-208.
[54]Yankner B, Dawes L, Fisher S, et al. Neurotoxicity of a fragment of the amyloid precursor associated with Alzheimer's disease [J]. Science,1989, 245(4916):417-420.
[55]Klein W L, Stine Jr W B, Teplow D B. Small assemblies of unmodified amyloid β-protein are the proximate neurotoxin in Alzheimer's disease [J]. Neurobiol. Aging,2004,25(5):569-580.
[56]Gemma C, Mark A S, Xiongwei Z, et al. Alzheimer disease:Evidence for a central pathogenic role of iron-mediated reactive oxygen species [J]. J. Alzheimers Dis.,2004,6(2):165-169.
[57]Hureau C, Faller P. AP-mediated ROS production by Cu ions:Structural insights, mechanisms and relevance to Alzheimer's disease [J]. Biochimie, 2009,91(10):1212-1217.
[58]Gong J, Sawamura N, Zou K, et al. Amyloid β-protein affects cholesterol metabolism in cultured neurons:Implications for pivotal role of cholesterol in the amyloid cascade [J]. J. Neurosci. Res.,2002,70(3):438-446.
[59]Atwood C S, Obrenovich M E, Liu T, et al. Amyloid-β:A chameleon walking in two worlds:A review of the trophic and toxic properties of amyloid-β [J]. Brain Res. Rev.,2003,43(1):1-16.
[60]Faller P, Hureau C. Bioinorganic chemistry of copper and zinc ions coordinated to amyloid-p peptide [J]. Dalton T.,2009,7:1080-1094.
[61]Stadtman E R, Moskovitz J, L. L R. Oxidation of methionine residues of proteins:Biological consequences [J]. Antioxid. Redox Signal.,2003,5:577-582.
[62]Luo Y, Sunderland T, Roth G S, et al. Physiological levels of β-amyloid peptide promote PC 12 cell proliferation [J]. Neurosci. Lett.,1996,217(2-3): 125-128.
[63]Plant L D, Boyle J P, Smith I F, et al. The production of amyloid β peptide is a critical requirement for the viability of central neurons [J]. J. Neurosci.,2003, 23(13):5531-5535.
[64]Gaggelli E, Kozlowski H, Valensin D, et al. Copper homeostasis and neurodegenerative disorders (Alzheimer's, prion, and Parkinson's diseases and amyotrophic lateral sclerosis) [J]. Chem. Rev.,2006,106(6):1995-2044.
[65]Adlard P A, Bush A I. Metals and Alzheimer's disease [J]. J. Alzheimers Dis., 2006,10(2):145-163.
[66]Zatta P, Drago D, Bolognin S, et al. Alzheimer's disease, metal ions and metal homeostatic therapy [J]. Trends Pharmacol. Sci.,2009,30(7):346-355.
[67]Hutchinson R W, Cox A G, McLeod C W, et al. Imaging and spatial distribution of β-amyloid peptide and metal ions in Alzheimer's plaques by laser ablation-inductively coupled plasma-mass spectrometry [J]. Anal. Biochem.,2005,346(2):225-233.
[68]Curtain C C, Ali F, Volitakis I, et al. Alzheimer's disease amyloid-β binds copper and zinc to generate an allosterically ordered membrane-penetrating structure containing superoxide dismutase-like subunits [J]. J. Biol. Chem., 2001,276(23):20466-20473.
[69]Atwood C S, Moir R D, Huang X, et al. Dramatic aggregation of Alzheimer AP by Cu(Ⅱ) is induced by conditions representing physiological acidosis [J]. J. Biol. Chem.,1998,273(21):12817-12826.
[70]Sarell C J, Wilkinson S R, Viles J H. Substoichiometric levels of Cu2+ ions accelerate the kinetics of fiber formation and promote cell toxicity of amyloid-β from Alzheimer disease [J]. J. Biol. Chem.,2010,285(53): 41533-41540.
[71]Bush A I, Tanzi R E. Therapeutics for Alzheimer's disease based on the metal hypothesis [J]. Neurotherapeutics,2008,5(3):421-432.
[72]Syme C D, Nadal R C, Rigby S E J, et al. Copper binding to the amyloid-P (Aβ) peptide associated with Alzheimer's disease [J]. J. Biol. Chem.,2004, 279(18):18169-18177.
[73]Guilloreau L, Damian L, Coppel Y, et al. Structural and thermodynamical properties of Cull amyloid β 16/28 complexes associated with Alzheimer's disease [J]. J. Biol. Inorg. Chem.,2006,11(8):1024-1038.
[74]Minicozzi V, Stellato F, Comai M, et al. Identifying the minimal copper-and zinc-binding site sequence in amyloid-β peptides [J]. J. Biol. Chem.,2008, 283(16):10784-10792.
[75]Hureau C, Coppel Y, Dorlet P, et al. Deprotonation of the Aspl-Ala2 peptide bond induces modification of the dynamic copper(Ⅱ) environment in the amyloid-β peptide near physiological pH [J]. Angew. Chem. Int. Ed.,2009, 48(50):9522-9525.
[76]Drew S C, Masters C L, Barnham K J. Alanine-2 carbonyl is an oxygen ligand in Cu2+ coordination of Alzheimer's disease amyloid-β peptide-relevance to N-terminally truncated forms [J]. J. Am. Chem. Soc.,2009,131(25): 8760-8761.
[77]Shin B, Saxena S. Direct evidence that all three histidine residues coordinate to Cu(Ⅱ) in amyloid-β1-16 [J]. Biochemistry,2008,47(35):9117-9123.
[78]Sarell C J, Syme C D, Rigby S E J, et al. Copper(Ⅱ) binding to amyloid-(3 fibrils of Alzheimer's disease reveals a picomolar affinity:stoichiometry and coordination geometry are independent of Aβ oligomeric form [J]. Biochemistry,2009,48(20):4388-4402.
[79]Dorlet P, Gambarelli S, Faller P, et al. Pulse EPR spectroscopy reveals the coordination sphere of copper(Ⅱ) ions in the 1-16 amyloid-βpeptide:A key role of the first two N-terminus residues [J]. Angewandte Chemie,2009, 121(49):9437-9440.
[80]Atwood C S, Scarpa R C, Huang X, et al. Characterization of copper interactions with Alzheimer amyloid β peptides:Identification of an attomolar-affinity copper binding site on amyloid β1-42 [J]. J. Neurochem., 2000,75:1219-1233.
[81]Garzon-Rodriguez W, Yatsimirsky A K, Glabe C G. Binding of Zn(Ⅱ), Cu(Ⅱ), and Fe(Ⅱ) ions to Alzheimer's Aβ peptide studied by fluorescence [J]. Bioorg. Med. Chem. Lett.,1999,9(15):2243-2248.
[82]Zawisza I, Rozga M, Bal W. Affinity of copper and zinc ions to proteins and peptides related to neurodegenerative conditions (Aβ, APP, a-synuclein, PrP) [J]. Coordin Chem. Rev.,2012,256(19-20):2297-2307.
[83]Rozga M, Bal W. The Cu(Ⅱ)/Aβ/human serum albumin model of control mechanism for copper-related amyloid neurotoxicity [J]. Chem. Res. Toxicol., 2010,23(2):298-308.
[84]Tougu V, Karafin A, Palumaa P. Binding of zinc(Ⅱ) and copper(Ⅱ) to the full-length Alzheimer's amyloid-p peptide [J]. J. Neurochem.,2008,104(5): 1249-1259.
[85]Rozga M, Protas A M, Jablonowska A, et al. The Cu(Ⅱ) complex of Aβ40 peptide in ammonium acetate solutions. Evidence for ternary species formation [J]. Chem. Commun.,2009,11:1374-1376.
[86]Xiao Z, Wedd A G. The challenges of determining metal-protein affinities [J]. Nat. Prod. Rep.,2010,27(5):768-789.
[87]Hatcher L Q, Hong L, Bush W D, et al. Quantification of the binding constant of copper(Ⅱ) to the amyloid-β peptide [J]. J. Phys. Chem. B,2008,112(27): 8160-8164.
[88]Kowalik-Jankowska T, Ruta M, Wisniewska K, et al. Coordination abilities of the 1-16 and 1-28 fragments of β-amyloid peptide towards copper(Ⅱ) ions:a combined potentiometric and spectroscopic study [J]. J. Inorg. Biochem.,2003, 95(4):270-282.
[89]Ma Q, Hu J, Wu W H, et al. Characterization of copper binding to the peptide amyloid-β(1-16) associated with Alzheimer's disease [J]. Biopolymers,2006, 83(1):20-31.
[90]Hong L, Bush W D, Hatcher L Q, et al. Determining thermodynamic parameters from isothermal calorimetric isotherms of the binding of macromolecules to metal cations originally chelated by a weak ligand [J]. J. Phys. Chem. B,2007,112(2):604-611.
[91]Maiti N C, Jiang D L, Wain A J, et al. Mechanistic studies of Cu(Ⅱ) binding to amyloid-β peptides and the fluorescence and redox behaviors of the resulting complexes [J]. J. Phys. Chem. B,2008,112(28):8406-8411.
[92]Banci L, Bertini I, Ciofi-Baffoni S, et al. Affinity gradients drive copper to cellular destinations [J]. Nature,2010,465(7298):645-648.
[93]Jiang D, Li X, Williams R, et al. Ternary complexes of iron, amyloid-β, and nitrilotriacetic acid:binding affinities, redox properties, and relevance to iron-induced oxidative stress in Alzheimer's disease [J]. Biochemistry,2009, 48(33):7939-7947.
[94]Gu Z, Zhong P, Yan Z. Activation of muscarinic receptors inhibits p-amyloid peptide-induced signaling in cortical slices [J]. J. Biol. Chem.,2003,278(19): 17546-17556.
[95]Mitchell R A, Herrmann N, Lanctot K L. The role of dopamine in symptoms and treatment of apathy in Alzheimer's disease [J]. CNS Neurosci. Ther.,2011, 17(5):411-427.
[96]Marien M R, Colpaert F C, Rosenquist A C. Noradrenergic mechanisms in neurodegenerative diseases:a theory [J]. Brain Res. Rev.,2004,45(1):38-78.
[97]Perez-Garcia G S, Meneses A. Effects of the potential 5-HT7 receptor agonist AS 19 in an autoshaping learning task [J]. Behav. Brain Res.,2005,163(1): 136-140.
[98]Andorn A C, Pappolla M A. Catecholamines inhibit lipid peroxidation in young, aged, and Alzheimer's disease brain [J]. Free Radical Biol. Med.,2001, 31(3):315-320.
[99]Opazo C. Metalloenzyme-like activity of Alzheimer's disease P-amyloid. Cu-dependent catalytic conversion of dopamine, cholesterol, and biological reducing agents to neurotoxic H2O2 [J]. J. Biol. Chem.,2002,277(43): 40302-40308.
[100]Huong V T, Shimanouchi T, Shimauchi N, et al. Catechol derivatives inhibit the fibril formation of amyloid-β peptides [J]. J. Biosci. Bioeng.,2010,109(6): 629-634.
[101]German D C, Manaye K F, White C L, et al. Disease-specific patterns of locus coeruleus cell loss [J]. Ann. Neurol.,1992,32(5):667-676.
[102]Heinonen E H, Savijarvi M, Kotila M. Effects of monoamine oxidase inhibition by selegline on concentration of noradrenaline and monoamine metabolites in CSF of patients with Alzheimer's disease [J]. J. Neuroal. Transm. Park. Dis. Dement. Sect.,1993,5(3):193-202.
[103]Martignoni E, Bono G, Blandini F. Monoamines and related metabolite levels in the cerebrospinal fluid of patients with dementia of Alzheimer type: Influence of treatment with L-depreny [J]. J. Neuroal. Transm. Park. Dis. Dement. Sect.,1991,3(1):15-25.
[104]Sakai N, Sasa M, Ishihara K. Effects of L-threo-DOPS, a noradrenaline precursor, on the long-term potentiation in the rat hippocampal mossy fiber-CA3 region [J]. Brain Res.,1991,20(2):267-273.
[105]Missnnier P, Ragot R, Derouesn C. Automatic attentional shifts induced by a noradrenerg ic drug in Alzheimer's disease:evidence from evoked potentials [J]. Int. J. Psychophysiol.,1999,33(3):243-251.
[106]Rauk A. The chemistry of Alzheimer's disease [J]. Chem. Soc. Rev.,2009, 38(9):2698-715.
[107]King M E, Kan H M, Baas P W, et al. Tau-dependent microtubule disassembly initiated by prefibrillar β-amyloid [J]. J. Cell Biol.,2006,175(4):541-546.
[108]Cedazo-Minguez A, Popescu B O, Blanco-Millan J M, et al. Apolipoprotein E and β-amyloid (1-42) regulation of glycogen synthase kinase-3β [J]. J. Neurochem.,2003,87(5):1152-1164.
[109]Sadowski M J, Pankiewicz J, Scholtzova H, et al. Blocking the apolipoprotein E/amyloid-β interaction as a potential therapeutic approach for Alzheimer's disease [J]. Proc. Natl. Acad. Sci. USA,2006,103(49):18787-18792.
[110]Hartmann T, Kuchenbecker J, Grimm M O W. Alzheimer's disease:the lipid connection [J]. J. Neurochem.,2007,103:159-170.
[111]Yao Z, Papadopoulos V. Function of β-amyloid in cholesterol transport:a lead to neurotoxicity [J]. FASEB J.,2002,16(12):1677-1679.
[112]Puglielli L, Friedlich A L, Setchell K D R, et al. Alzheimer disease β-amyloid activity mimics cholesterol oxidase [J]. J. Clin. Invest.,2005,115(9): 2556-2563.
[113]Shimanouchi T, Tasaki M, Vu H T, et al. Aβ/Cu-catalyzed oxidation of cholesterol in 1,2-dipalmitoyl phosphatidylcholine liposome membrane [J]. J. Biosci. Bioeng.,2010,109(2):145-148.
[114]Milton N G. Amyloid-β binds catalase with high affinity and inhibits hydrogen peroxide breakdown [J]. Biochem. J,1999,344:293-296.
[115]赵晓君,陈焕文,宋大千等,表面等离子体子共振传感器1：基本原理[J],分析仪器,2000,4：1-8。
[116]http://www.biosensingusa.com/BI-3000.html
[117]Lovell M A, Robertson J D, Teesdale W J, et al. Copper, iron and zinc in Alzheimer's disease senile plaques [J]. J. Neurol. Sci.,1998,158(1):47-52.
[118]Pecci L, Montefoschi G, Cavallini D. Some new details of the copper-hydrogen peroxide interaction. [J]. Biochem. Biophys. Res. Co.,1997, 235:264-267.
[119]Atwood C S, Perry G, Zeng H, et al. Copper mediates dityrosine cross-linking of Alzheimer's amyloid-β[J]. Biochemistry,2003,43(2):560-568.
[120]Dikalov S I, Vitek M P, Mason R P. Cupric-amyloid β peptide complex stimulates oxidation of ascorbate and generation of hydroxyl radical [J]. Free Radical Biol. Med.,2004,36(3):340-347.
[121]Guilloreau L, Combalbert S, Sournia-Saquet A, et al. Redox chemistry of copper-amyloid-β:The generation of hydroxyl radical in the presence of ascorbate is linked to redox-potentials and aggregation state [J]. ChemBioChem,2007,8(11):1317-1325.
[122]Pithadia A S, Lim M H. Metal-associated amyloid-β species in Alzheimer's disease [J]. Curr. Opin. Chem. Biol.,2012,16(1-2):67-73.
[123]Yoshiike Y, Tanemura K, Murayama O, et al. New insights on how metals disrupt amyloid β-aggregation and their effects on amyloid-p cytotoxicity [J]. J. Biol. Chem.,2001,276(34):32293-32299.
[124]Miura T, Suzuki K, Kohata N, et al. Metal binding modes of Alzheimer's amyloid β-peptide in insoluble aggregates and soluble complexes [J]. Biochemistry,2000,39(23):7024-7031.
[125]Suzuki K, Miura T, Takeuchi H. Inhibitory effect of Copper(Ⅱ) on Zinc(Ⅱ)-induced aggregation of amyloid β-peptide [J]. Biochem. Biophys. Res. Co.,2001,285(4):991-996.
[126]Ali-Torres J, Marechal J-D, Rodriguez-Santiago L, et al. Three dimensional models of Cu2+-Aβ(1-16) complexes from computational approaches [J]. J. Am. Chem. Soc.,2011,133(38):15008-15014.
[127]Grant S A, Bettencourt K, Krulevitch P, et al. In vitro and in vivo measurements of fiber optic and electrochemical sensors to monitor brain tissue pH [J]. Sensor. Actuator. B:Chemical,2001,72(2):174-179.
[128]Su Y, Chang P T. Acidic pH promotes the formation of toxic fibrils from β-amyloid peptide [J]. Brain Res.,2001,893(1-2):287-291.
[129]Harguindey S, Reshkin S J, Orive G, et al. Growth and trophic factors, pH and the Na+/H+ exchanger in Alzheimer's disease, other neurodegenerative diseases and cancer:New therapeutic possibilities and potential dangers [J]. Curr. Alzheimer Res.,2007,4(1):53-65.
[130]Jiang D, Men L, Wang J, et al. Redox reactions of copper complexes formed with different β-amyloid peptides and their neuropathalogical relevance [J]. Biochemistry,2007,46(32):9270-9282.
[131]Xin Y, Gao Y, Guo J, et al. Real-time detection of Cu2+ sequestration and release by immobilized apo-metallothioneins using SECM combined with SPR [J]. Biosens. Bioelectron.,2008,24(3):369-375.
[132]Myszka D G. Kinetic analysis of macromolecular interactions using surface plasmon resonance biosensors [J]. Curr. Opin. Biotech.,1997,8(1):50-57.
[133]Bin Y, Chen S, Xiang J. pH-dependent kinetics of copper ions binding to amyloid-β peptide [J]. J. Inorg. Biochem.,2013,119:21-27.
[134]O'shannessy D J, Brighamburke M, Soneson K K, et al. Determination of rate and equilibrium binding constants for macromolecular interactions using surface plasmon resonance:use of nonlinear least squares analysis methods [J]. Anal. Biochem.,1993,212(2):457-468.
[135]Wegner G J, Wark A W, Lee H J, et al. Real-time surface plasmon resonance imaging measurements for the multiplexed determination of protein adsorption/desorption kinetics and surface enzymatic reactions on peptide microarrays [J]. Anal. Chem.,2004,76(19):5677-5684.
[136]Manevich Y, Held K D, Biaglow J E. Coumarin-3-carboxylic acid as a detector for hydroxyl radicals generated chemically and by gamma radiation [J]. Radiat. Res.,1997,148(6):580-591.
[137]Nadal R C, Rigby S E J, Viles J H. Amyloid β-Cu2+ complexes in both monomeric and fibrillar forms do not generate H2O2 catalytically but quench hydroxyl radicals [J]. Biochemistry,2008,47(44):11653-11664.
[138]Huang E, Zhou F, Deng L. Studies of surface coverage and orientation of DNA molecules immobilized onto preformed alkanethiol self-assembled monolayers [J]. Langmuir,2000,16(7):3272-3280.
[139]Su X, O'Shea S J. Determination of monoenzyme-and bienzyme-stimulated precipitation by a cuvette-based surface plasmon resonance instrument [J]. Anal. Biochem.,2001,299(2):241-246.
[140]Thakur G, Micic M, Leblanc R M. Surface chemistry and spectroscopy of amyloid β (1-42) mixed with and conjugated to quantum dots langmuir monolayer [J]. J. Phys. Chem. C,2010,114(35):15084-15093.
[141]Martell A E, Smith R M. NIST Standard Reference Database 46.2004, version 8.0.
[142]Chen W T, Liao Y H, Yu H M, et al. Distinct effects of Zn2+, Cu2+, Fe3+, and Al3+ on amyloid-P stability, oligomerization, and aggregation:amyloid-β destabilization promotes annular protofibril formation [J]. J. Biol. Chem., 2011,286(11):9646-9656.
[143]Smith D G, Cappai R, Barnham K J. The redox chemistry of the Alzheimer's disease amyloid β peptide [J]. Biochim. Biophys. Acta.,2007,1768(8): 1976-1990.
[144]Rozga M, Sokolowska M, Protas A, et al. Human serum albumin coordinates Cu(Ⅱ) at its N-terminal binding site with 1 pM affinity [J]. J. Biol. Inorg. Chem.,2007,12(6):913-918.
[145]Jiang D, Li X, Gargey Y, et al. Reaction rates and mechanism of the ascorbic acid oxidation by molecular oxygen facilitated by Cu(Ⅱ)-containing amyloid-β complexes and aggregates. [J]. J. Phys. Chem. B,2010,114(14):4896-4903.
[146]Kowalewski T, Holtzman D M. In situ atomic force microscopy study of Alzheimer's P-amyloid peptide on different substrates:New insights into mechanism of p-sheet formation [J]. Proc. Natl. Acad. Sci. USA,1999,96(7): 3688-3693.
[147]Smith D P, Ciccotosto G D, Tew D J, et al. Concentration dependent Cu2+ induced aggregation and dityrosine formation of the Alzheimer's disease amyloid-β peptide [J]. Biochemistry,2007,46(10):2881-2891.
[148]Manevich Y, Held K D, Biaglow J E. Coumarin-3-carboxylic acid as a detector for hydroxyl radicals generated chemically and by gamma radiation [J]. Radi. Res.,1997,148(6):580-591.
[149]Ciccotosto G D, Tew D J, Fodero-Tavoletti M T, et al. Concentration dependent Cu(Ⅱ) induced aggregation and dityrosine formation of the Alzheimer's disease Amyloid-β peptide [J]. Biochemistry,2007,46(10): 2881-2891.
[150]Nakamura M, Shishido N, Nunomura A, et al. Three histidine residues of amyloid-β peptide control the redox activity of copper and iron [J]. Biochemistry,2007,46(44):12737-12743.
[151]Anwar Z M, Azab H A. Ternary complexes in solution, comparison of the coordination tendency of some biologically important zwitterionic buffers toward the binary complexes of some transition metal ions and some amino acids [J]. J. Chem. Eng. Data,1999,44(6):1151-1157.
[152]Shin B, Saxena S. Substantial contribution of the two imidazole rings of the His13-His14 dyad to Cu(Ⅱ) binding in amyloid-β(1-16) at physiological pH and its significance [J]. J. Phys. Chem. A,2011,115(34):9590-9602.
[153]Righetti P G, Magnusdottir S, Gelfi C, et al. Behaviour of inorganic and organic cations in the Debye-Hiickel layer of DNA [J]. J. Chromatogr. A, 2001,920(1-2):309-316.
[154]Sun M, Chen J, Liu X H, et al. Molecular interaction modeling of Ser-His dipeptide and buffers [J]. J. Mol. Struc. (Theochem),2004,668(1):47-49.
[155]Quan L, Wei D, Jiang X, et al. Resurveying the Tris buffer solution:The specific interaction between tris(hydroxymethyl)aminomethane and lysozyme [J]. Anal. Biochem.,2008,378(2):144-150.
[156]Taha M, Lee M. Interactions of TRIS tris(hydroxymethyl)aminomethane and related buffers with peptide backbone:Thermodynamic characterization [J]. Phys. Chem. Chem. Phys.,2010,12(39):12840-12850.
[157]Wang Q, Shah N, Zhao J, et al. Structural, morphological, and kinetic studies of β-amyloid peptide aggregation on self-assembled monolayers [J]. Phys. Chem. Chem. Phys.,2011,13(33):15200-15210.
[158]Bin Y, Gao Y, Xiang J, et al. Immobilization of metallothionein on highly oriented pyrolytic graphite for biosensor design [J]. Surf. Interface Anal.,2009, 41:834-838.
[159]Shakked Z, Viswamitra M A, Kennard O. Interactions of tris buffer with nucleotides:The crystal structure of tris(hydroxymethyl)methylammonium adenosine 5'-diphosphate dihydrate [J]. Biochemistry,1980,19(12): 2567-2571.
[160]Compagnini A, Cunsolo V, Foti S, et al. Improved accuracy in the matrix-assisted laser desorption/ionization-mass spectrometry determination of the molecular mass of cyanogen bromide fragments of proteins by post-cleavage reaction with tris(hydroxymethyl)aminomethane [J]. Proteomics, 2001,1(8):967-974.
[161]Burcham P C, Fontaine F R, Petersen D R, et al. Reactivity with tris(hydroxymethyl)aminomethane confounds immunodetection of acrolein-adducted proteins [J]. Chem. Res. Toxicol.,2003,16(10):1196-1201.
[162]Williams D E, Reisfeld R A. Disc electrophoresis in polyacrylamide gels: Extension to new conditions of pH and buffer [J]. Ann. NY Acad. Sci.,1964, 121(2):373-381.
[163]Reinikainen K J, Soininen H, Riekkinen P J. Neurotransmitter changes in alzheimer's disease:Implications to diagnostics and therapy [J]. J. Neurosci. Res.,1990,27(4):576-586.
[164]Selkoe D J. Alzheimer's disease is a synaptic failure [J]. Science,2002, 298(5594):789-791.
[165]Chimon S, Shaibat M A, Jones C R, et al. Evidence of fibril-like β-sheet structures in a neurotoxic amyloid intermediate of Alzheimer's β-amyloid [J]. Nat. Struct. Mol. Biol.,2007,14(12):1157-1164.
[166]Kayed R, Head E, Thompson J L, et al. Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis [J]. Science,2003, 300(5618):486-489.
[167]Deshpande A, Mina E, Glabe C, et al. Different conformations of amyloid β induce neurotoxicity by distinct mechanisms in human cortical neurons [J]. J. Neurosci.,2006,26(22):6011-6018.
[168]Guzman-Ramos K, Moreno-Castilla P, Castro-Cruz M, et al. Restoration of dopamine release deficits during object recognition memory acquisition attenuates cognitive impairment in a triple transgenic mice model of Alzheimer's disease [J]. Learn. Memory,2012,19(10):453-460.
[169]Li J, Zhu M, B. M-B A, et al. Dopamine and L-dopa disaggregate amyloid fibrils:implications for Parkinson's and Alzheimer's disease [J]. FASEB J. 2004,18:962-964.
[170]Fu W, Luo H, Parthasarathy S, et al. Catecholamines potentiate amyloid (3-peptide neurotoxicity:Involvement of oxidative stress, mitochondrial dysfunction, and perturbed calcium homeostasis [J]. Neurobiol. Dis.,1998, 5(4):229-243.
[171]Guzman-Ramos K, Moreno-Castilla P, Castro-Cruz M, et al. Restoration of dopamine release deficits during object recognition memory acquisition attenuates cognitive impairment in a triple transgenic mice model of Alzheimer's disease [J]. Learn. Memory,2012,19(10):453-460.
[172]Di Giovanni S, Eleuteri S, Paleologou K E, et al. Entacapone and tolcapone, two catechol O-methyltransferase inhibitors, block fibril formation of α-synuclein and β-amyloid and protect against amyloid-induced toxicity [J]. J. Biol. Chem.,2010,285(20):14941-14954.
[173]Liu J, Mori A. Monoamine metabolism provides an antioxidant defense in the brain against oxidant-and free radical-induced damage [J]. Arch. Biochem. Biophys.,1993,302(1):118-127.
[174]Wen X, Jia Y, Liu Z. Micellar effects on the electrochemistry of dopamine and its selective detection in the presence of ascorbic acid [J]. Talanta,1999,50(5): 1027-1033.
[175]Michel P P, Hefti F. Toxicity of 6-hydroxydopamine and dopamine for dopaminergic neurons in culture [J]. J. Neurosci. Res.,1990,26(4):428-435.
[176]De Felice F G, Houzel J C, Garcia-Abreu J, et al. Inhibition of Alzheimer's disease β-amyloid aggregation, neurotoxicity, and in vivo deposition by nitrophenols:implications for Alzheimer's therapy [J]. FASEB J.,2001,15(7): 1297-1299.
[177]Foote S L, Bloom F E, Aston-Jones G. Nucleus locus ceruleus:new evidence of anatomical and physiological specificity [J]. Physiol. Rev.,1983,63(3): 844-914.
[178]Kong Y, Ruan L, Qian L, et al. Norepinephrine promotes microglia to uptake and degrade amyloid β peptide through upregulation of mouse formyl peptide receptor 2 and induction of insulin-degrading enzyme [J]. J. Neurosci.,2010, 30(35):11848-11857.