早期检测阿尔茨海默病的生物标志物新型仿生受体
|
摘要
背景:如何对阿尔茨海默病实现早期诊断和精确诊断目前仍然是一个难题,大量患者因为确诊过晚或误诊而延误治疗时间。针对阿尔茨海默病生物标志物的检测仍然缺乏灵敏、高效、低成本的手段,所以相关生物分析方法的开发与改进显得尤为重要。目的:简述阿尔茨海默病的诊断方法和相关生物标志物,归纳总结应用于阿尔茨海默病生物标志物早期检测新型仿生受体的研究进展。方法:应用计算机检索PubMed数据库、CNKI和万方数据库2000至2016年收录的,关于阿尔茨海默病生物标志物及其检测方法的文章,以"阿尔茨海默病、生物标志物、检测"或"Alzheimer’s disease,biomarkers,detect/detecting/detection"为检索词,最终选择40篇文章进行分析和综述。结果与结论:现阶段针对阿尔茨海默病生物标志物所采用的生物分析手段多以抗体作为生物标志物的识别和捕捉元件,但用传统抗体作为检测受体有一定局限性。因此,可采用新型仿生受体替换传统检测抗体,其具有对目标分析物识别特异性高、尺寸更小、化学修饰过程更简便、生产成本更低、产品稳定性更高及所能匹配的目标分析物范围更广等优势。针对蛋白类物质分析所开发的仿生受体包括核酸适配体、多肽受体、类肽受体、分子印迹聚合物、纳米抗体、凝溶胶蛋白和瓜环类化合物等。采用新型仿生受体替代传统抗体进行生物标志物检测,将提高阿尔茨海默病诊断的及时性和准确性。
BACKGROUND: It is still a problem to achieve early and accurate diagnosis of Alzheimer's disease, and delayed treatments often occur in a large number of patients because of late diagnosis or misdiagnosis. Therefore, the development and improvement of related bioanalytical methods are of great importance for the biomarker detection of Alzheimer's disease which is still lack of means that are sensitive, efficient and low-cost. OBJECTIVE: To summarize the diagnostic methods and related biomarkers of Alzheimer's disease, and to sum up the research progress in novel biomimetic receptors for the early detection of Alzheimer's disease biomarkers. METHODS: PubMed, CNKI and Wanfang databases were used to search articles related to the biomarker studies of Alzheimer's disease and relevant studies about methods of biomarkers detection published from 2000 to 2016. The key words were "Alzheimer's disease, biomarkers, detect/detecting/detection" in Chinese and English, respectively. Finally 40 articles were obtained for the review. RESULTS AND CONCLUSION: At present, the bioanalytical methods used for biomarker detection of Alzheimer's disease mostly utilize antibodies as recognition and capture elements of biomarkers, but there are some limitations using traditional antibodies as detection receptors. Thus, novel biomimetic receptors can be substituted for conventional antibodies. Novel biomimetic receptors have high specificity, small size, low production costs and high product stability, and their chemical modification process is relatively convenient. Biomimetic receptors developed for protein analysis include aptamers, polypeptide receptors, peptoid receptors, molecularly imprinted polymers, nanobodies, gelsolin and cucurbit urils. Detection of biomarkers with novel biomimetic receptors instead of conventional antibodies will be more accurate and timely in the early diagnosis of Alzheimer's disease.
BACKGROUND: It is still a problem to achieve early and accurate diagnosis of Alzheimer's disease, and delayed treatments often occur in a large number of patients because of late diagnosis or misdiagnosis. Therefore, the development and improvement of related bioanalytical methods are of great importance for the biomarker detection of Alzheimer's disease which is still lack of means that are sensitive, efficient and low-cost. OBJECTIVE: To summarize the diagnostic methods and related biomarkers of Alzheimer's disease, and to sum up the research progress in novel biomimetic receptors for the early detection of Alzheimer's disease biomarkers. METHODS: PubMed, CNKI and Wanfang databases were used to search articles related to the biomarker studies of Alzheimer's disease and relevant studies about methods of biomarkers detection published from 2000 to 2016. The key words were "Alzheimer's disease, biomarkers, detect/detecting/detection" in Chinese and English, respectively. Finally 40 articles were obtained for the review. RESULTS AND CONCLUSION: At present, the bioanalytical methods used for biomarker detection of Alzheimer's disease mostly utilize antibodies as recognition and capture elements of biomarkers, but there are some limitations using traditional antibodies as detection receptors. Thus, novel biomimetic receptors can be substituted for conventional antibodies. Novel biomimetic receptors have high specificity, small size, low production costs and high product stability, and their chemical modification process is relatively convenient. Biomimetic receptors developed for protein analysis include aptamers, polypeptide receptors, peptoid receptors, molecularly imprinted polymers, nanobodies, gelsolin and cucurbit urils. Detection of biomarkers with novel biomimetic receptors instead of conventional antibodies will be more accurate and timely in the early diagnosis of Alzheimer's disease.
引文
[1]Heneka MT,Golenbock DT,Latz E.Innate immunity in Alzheimer's disease.Nat Immunol.2015;16(3):229-236.
[2]Walji AM,Hostetler ED,Selnick H,et al.Discovery of6-(Fluoro-18 F)-3-(1 H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine([18F]-MK-6240):A Positron Emission Tomography(PET)Imaging Agent for Quantification of Neurofibrillary Tangles(NFTs).J Med Chem.2016;59(10):4778-4789.
[3]Barage SH,Sonawane KD.Amyloid cascade hypothesis:Pathogenesis and therapeutic strategies in Alzheimer's disease.Neuropeptides.2015;52:1-18.
[4]Hansson O,Zetterberg H,Buchhave P,et al.Association between CSF biomarkers and incipient Alzheimer's disease in patients with mild cognitive impairment:a follow-up study.Lancet Neurol.2006;5(3):228-234.
[5]Shi XD,Sun K,Hu R,et al.Blocking the Interaction between Eph B2 and ADDLs by a Small Peptide Rescues Impaired Synaptic Plasticity and Memory Deficits in a Mouse Model of Alzheimer's Disease.J Neurosci.2016;36(47):11959-11973.
[6]Chen Y,Kong D,Liu L,et al.Development of an enzyme-linked immunosorbent assay(ELISA)for natamycin residues in foods based on a specific monoclonal antibody.Anal Methods-UK.2015;7(8):3559-3565.
[7]Gupta V,Davancaze T,Good J,et al.Bioanalytical qualification of clinical biomarker assays in plasma using a novel multi-analyte Simple Plex?platform.Bioanalysis.2016;8(23):2415-2428.
[8]Chiasserini D,Biscetti L,Farotti L,et al.Performance Evaluation of an Automated ELISA System for Alzheimer’s Disease Detection in Clinical Routine.J Alzheimers Dis.2016;54(1):55-67.
[9]Cowen T,Karim K,Piletsky S.Computational approaches in the design of synthetic receptors–A review.Anal Chim Acta.2016;936:62-74.
[10]Kunath S,Panagiotopoulou M,Maximilien J,et al.Cell and tissue imaging with molecularly imprinted polymers as plastic antibody mimics.Adv Healthc Mater.2015;4(9):1322-1326.
[11]Li S,Yang K,Liu J,et al.Surface-Imprinted Nanoparticles Prepared with a His-Tag-Anchored Epitope as the Template.Anal Chem.2015;87(9):4617-4620.
[12]Yang X,Dong X,Zhang K,et al.A molecularly imprinted polymer as an antibody mimic with affinity for lysine acetylated peptides.J Mater Chem B.2016;4(5):920-928.
[13]Rossetti C,Abdel QA,Halvorsen TG,et al.Antibody-free biomarker determination:Exploring molecularly imprinted polymers for pro-gastrin releasing peptide.Anal Chem.2014;86(24):12291-12298.
[14]Schirhagl R.Bioapplications for molecularly imprinted polymers.Anal Chem.2013;86(1):250-261.
[15]管习文,李欣怡,周琪,等.分子印迹聚合物的制备与应用进展[J].胶体与聚合物,2015,33(2):88-92.
[16]Toh SY,Citartan M,Gopinath SCB,et al.Aptamers as a replacement for antibodies in enzyme-linked immunosorbent assay.Biosens Bioelectron.2015;64:392-403.
[17]Scognamiglio V,Antonacci A,Lambreva MD,et al.Synthetic biology and biomimetic chemistry as converging technologies fostering a new generation of smart biosensors.Biosens Bioelectron.2015;74:1076-1086.
[18]Ylera F,Lurz R,Erdmann VA,et al.Selection of RNA aptamers to the Alzheimer's disease amyloid peptide.Biochem Bioph Res Co.2002;290(5):1583-1588.
[19]Sarell CJ,Karamanos TK,White SJ,et al.Distinguishing closely related amyloid precursors using an RNA aptamer.J Biol Chem.2014;289(39):26859-26871.
[20]Tannenberg R,Lauridsen L,Kanwar J,et al.Nucleic acid aptamers as novel class of therapeutics to mitigate Alzheimer's disease pathology.Curr Alzheimer Res.2013;10(4):442-448.
[21]Hamaguchi N,Ellington A,Stanton M.Aptamer beacons for the direct detection of proteins.Anal Biochem.2001;294(2):126-131.
[22]Randviir EP,Banks CE.Electrochemical impedance spectroscopy:an overview of bioanalytical applications.Anal Methods-UK.2013;5(5):1098-1115.
[23]Apostol MI,Perry K,Surewicz WK.Crystal structure of a human prion protein fragment reveals a motif for oligomer formation.J Am Chem Soc.2013;135(28):10202-10205.
[24]尹文超,曹云鹏.朊病毒蛋白样作用的β淀粉样蛋白[J].国际神经病学神经外科学杂志,2016,43(2):161-164.
[25]Chen S,Yadav SP,Surewicz WK.Interaction between human prion protein and amyloid-β(aβ)oligomers role of N-terminal residues.J Biol Chem.2010;285(34):26377-26383.
[26]Rushworth JV,Ahmed A,Griffiths HH,et al.A label-free electrical impedimetric biosensor for the specific detection of Alzheimer's amyloid-beta oligomers.Biosens Bioelectron.2014;56:83-90.
[27]Liu L,Xia N,Jiang M,et al.Electrochemical detection of amyloid-βoligomer with the signal amplification of alkaline phosphatase plus electrochemical-chemical-chemical redox cycling.J Electroanal Chem.2015;754:40-45.
[28]Sun J,Zuckermann RN.Peptoid polymers:a highly designable bioinspired material.ACS Nano.2013;7(6):4715-4732.
[29]Zhao Z,Zhu L,Bu X,et al.Label-free detection of Alzheimer’s disease through the ADP3 peptoid recognizing the serum amyloid-beta42 peptide.Chem Commun.2015;51(4):718-721.
[30]Yu Y,Zhang L,Li C,et al.A Method for Evaluating the Level of Solubleβ-Amyloid(1–40/1–42)in Alzheimer’s Disease Based on the Binding of Gelsolin toβ-Amyloid Peptides.Angew Chem Int Edit.2014;126(47):13046-13049.
[31]Ganesh HVS,Chow AM,Kerman K.Recent advances in biosensors for neurodegenerative disease detection.Trac-Trend Anal Chem.2016;79:363-370.
[32]Yu Y,Sun X,Tang D,et al.Gelsolin boundβ-amyloid peptides(1-40/1-42):Electrochemical evaluation of levels of soluble peptide associated with Alzheimer's disease.Biosens Bioelectron.2015;68:115-121.
[33]Ji L,Zhao X,Hua Z.Potential Therapeutic Implications of Gelsolin in Alzheimer's Disease.J Alzheimers Dis.2015;44(1):13-25.
[34]Muyldermans S.Nanobodies:natural single-domain antibodies.Annu Rev Biochem.2013;82:775-797.
[35]潘欣,潘伯驹,蔡家麟,等.单域抗体研究进展[J].生命科学,2012,24(5):404-410.
[36]Kasturirangan S,Li L,Emadi S,et al.Nanobody specific for oligomeric beta-amyloid stabilizes nontoxic form.Neurobiol Aging.2012;33(7):1320-1328.
[37]Williams SM,Schulz P,Sierks MR.Oligomericα-synuclein andβ-amyloid variants as potential biomarkers for Parkinson's and Alzheimer's diseases.Eur J Neurosci.2016;43(1):3-16.
[38]Isaacs L.Cucurbit[n]urils:from mechanism to structure and function.Chem Commun.2009;(6):619-629.
[39]Li H,Xie H,Cao Y,et al.A general way to assay protein by coupling peptide with signal reporter via supermolecule formation.Anal Chem.2012;85(2):1047-1052.
[40]张宁强,黄晓玲,班琳哲,等.葫芦[n]脲应用研究进展[J].化学进展,2014,27(2/3):192-211.
[2]Walji AM,Hostetler ED,Selnick H,et al.Discovery of6-(Fluoro-18 F)-3-(1 H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine([18F]-MK-6240):A Positron Emission Tomography(PET)Imaging Agent for Quantification of Neurofibrillary Tangles(NFTs).J Med Chem.2016;59(10):4778-4789.
[3]Barage SH,Sonawane KD.Amyloid cascade hypothesis:Pathogenesis and therapeutic strategies in Alzheimer's disease.Neuropeptides.2015;52:1-18.
[4]Hansson O,Zetterberg H,Buchhave P,et al.Association between CSF biomarkers and incipient Alzheimer's disease in patients with mild cognitive impairment:a follow-up study.Lancet Neurol.2006;5(3):228-234.
[5]Shi XD,Sun K,Hu R,et al.Blocking the Interaction between Eph B2 and ADDLs by a Small Peptide Rescues Impaired Synaptic Plasticity and Memory Deficits in a Mouse Model of Alzheimer's Disease.J Neurosci.2016;36(47):11959-11973.
[6]Chen Y,Kong D,Liu L,et al.Development of an enzyme-linked immunosorbent assay(ELISA)for natamycin residues in foods based on a specific monoclonal antibody.Anal Methods-UK.2015;7(8):3559-3565.
[7]Gupta V,Davancaze T,Good J,et al.Bioanalytical qualification of clinical biomarker assays in plasma using a novel multi-analyte Simple Plex?platform.Bioanalysis.2016;8(23):2415-2428.
[8]Chiasserini D,Biscetti L,Farotti L,et al.Performance Evaluation of an Automated ELISA System for Alzheimer’s Disease Detection in Clinical Routine.J Alzheimers Dis.2016;54(1):55-67.
[9]Cowen T,Karim K,Piletsky S.Computational approaches in the design of synthetic receptors–A review.Anal Chim Acta.2016;936:62-74.
[10]Kunath S,Panagiotopoulou M,Maximilien J,et al.Cell and tissue imaging with molecularly imprinted polymers as plastic antibody mimics.Adv Healthc Mater.2015;4(9):1322-1326.
[11]Li S,Yang K,Liu J,et al.Surface-Imprinted Nanoparticles Prepared with a His-Tag-Anchored Epitope as the Template.Anal Chem.2015;87(9):4617-4620.
[12]Yang X,Dong X,Zhang K,et al.A molecularly imprinted polymer as an antibody mimic with affinity for lysine acetylated peptides.J Mater Chem B.2016;4(5):920-928.
[13]Rossetti C,Abdel QA,Halvorsen TG,et al.Antibody-free biomarker determination:Exploring molecularly imprinted polymers for pro-gastrin releasing peptide.Anal Chem.2014;86(24):12291-12298.
[14]Schirhagl R.Bioapplications for molecularly imprinted polymers.Anal Chem.2013;86(1):250-261.
[15]管习文,李欣怡,周琪,等.分子印迹聚合物的制备与应用进展[J].胶体与聚合物,2015,33(2):88-92.
[16]Toh SY,Citartan M,Gopinath SCB,et al.Aptamers as a replacement for antibodies in enzyme-linked immunosorbent assay.Biosens Bioelectron.2015;64:392-403.
[17]Scognamiglio V,Antonacci A,Lambreva MD,et al.Synthetic biology and biomimetic chemistry as converging technologies fostering a new generation of smart biosensors.Biosens Bioelectron.2015;74:1076-1086.
[18]Ylera F,Lurz R,Erdmann VA,et al.Selection of RNA aptamers to the Alzheimer's disease amyloid peptide.Biochem Bioph Res Co.2002;290(5):1583-1588.
[19]Sarell CJ,Karamanos TK,White SJ,et al.Distinguishing closely related amyloid precursors using an RNA aptamer.J Biol Chem.2014;289(39):26859-26871.
[20]Tannenberg R,Lauridsen L,Kanwar J,et al.Nucleic acid aptamers as novel class of therapeutics to mitigate Alzheimer's disease pathology.Curr Alzheimer Res.2013;10(4):442-448.
[21]Hamaguchi N,Ellington A,Stanton M.Aptamer beacons for the direct detection of proteins.Anal Biochem.2001;294(2):126-131.
[22]Randviir EP,Banks CE.Electrochemical impedance spectroscopy:an overview of bioanalytical applications.Anal Methods-UK.2013;5(5):1098-1115.
[23]Apostol MI,Perry K,Surewicz WK.Crystal structure of a human prion protein fragment reveals a motif for oligomer formation.J Am Chem Soc.2013;135(28):10202-10205.
[24]尹文超,曹云鹏.朊病毒蛋白样作用的β淀粉样蛋白[J].国际神经病学神经外科学杂志,2016,43(2):161-164.
[25]Chen S,Yadav SP,Surewicz WK.Interaction between human prion protein and amyloid-β(aβ)oligomers role of N-terminal residues.J Biol Chem.2010;285(34):26377-26383.
[26]Rushworth JV,Ahmed A,Griffiths HH,et al.A label-free electrical impedimetric biosensor for the specific detection of Alzheimer's amyloid-beta oligomers.Biosens Bioelectron.2014;56:83-90.
[27]Liu L,Xia N,Jiang M,et al.Electrochemical detection of amyloid-βoligomer with the signal amplification of alkaline phosphatase plus electrochemical-chemical-chemical redox cycling.J Electroanal Chem.2015;754:40-45.
[28]Sun J,Zuckermann RN.Peptoid polymers:a highly designable bioinspired material.ACS Nano.2013;7(6):4715-4732.
[29]Zhao Z,Zhu L,Bu X,et al.Label-free detection of Alzheimer’s disease through the ADP3 peptoid recognizing the serum amyloid-beta42 peptide.Chem Commun.2015;51(4):718-721.
[30]Yu Y,Zhang L,Li C,et al.A Method for Evaluating the Level of Solubleβ-Amyloid(1–40/1–42)in Alzheimer’s Disease Based on the Binding of Gelsolin toβ-Amyloid Peptides.Angew Chem Int Edit.2014;126(47):13046-13049.
[31]Ganesh HVS,Chow AM,Kerman K.Recent advances in biosensors for neurodegenerative disease detection.Trac-Trend Anal Chem.2016;79:363-370.
[32]Yu Y,Sun X,Tang D,et al.Gelsolin boundβ-amyloid peptides(1-40/1-42):Electrochemical evaluation of levels of soluble peptide associated with Alzheimer's disease.Biosens Bioelectron.2015;68:115-121.
[33]Ji L,Zhao X,Hua Z.Potential Therapeutic Implications of Gelsolin in Alzheimer's Disease.J Alzheimers Dis.2015;44(1):13-25.
[34]Muyldermans S.Nanobodies:natural single-domain antibodies.Annu Rev Biochem.2013;82:775-797.
[35]潘欣,潘伯驹,蔡家麟,等.单域抗体研究进展[J].生命科学,2012,24(5):404-410.
[36]Kasturirangan S,Li L,Emadi S,et al.Nanobody specific for oligomeric beta-amyloid stabilizes nontoxic form.Neurobiol Aging.2012;33(7):1320-1328.
[37]Williams SM,Schulz P,Sierks MR.Oligomericα-synuclein andβ-amyloid variants as potential biomarkers for Parkinson's and Alzheimer's diseases.Eur J Neurosci.2016;43(1):3-16.
[38]Isaacs L.Cucurbit[n]urils:from mechanism to structure and function.Chem Commun.2009;(6):619-629.
[39]Li H,Xie H,Cao Y,et al.A general way to assay protein by coupling peptide with signal reporter via supermolecule formation.Anal Chem.2012;85(2):1047-1052.
[40]张宁强,黄晓玲,班琳哲,等.葫芦[n]脲应用研究进展[J].化学进展,2014,27(2/3):192-211.