摘要
阿尔茨海默病(AD)是一种广泛存在的痴呆症,据估计影响到全世界4440万人。AD的病理与淀粉样β(Aβ)肽在纤维和瘟疫中的积累密切相关,在Aβ肽聚集过程中形成的小寡聚中间种表现出最高的神经毒性。本文综述了Aβ肽电化学表征的最新进展。A型β肽在玻碳电极上的氧化,根据氨基酸序列、长度和含量的不同,分一、两步进行。第一个电子转移反应与酪氨酸Tyr 10氨基酸残基氧化反应相对应,第二个反应对应于三个组氨酸(His6、His 13和His 14)和一个蛋氨酸(Met35)氨基酸残基。通过电活性氨基酸氧化峰电流的降低,电化学检测Aβ肽的聚集和淀粉样纤维的形成。原子力显微镜观察到,Aβ肽的氧化还原行为与初始随机螺旋结构中Aβ肽单体的吸附形态变化有关,即Aβ肽单体在随机螺旋结构中或在α螺旋构象中形成聚集体、原纤维和两种纤维,对应于Aβ肽的β-片状结构。本文还讨论了以金属离子(特别是锌、铜、铁)相互作用为媒介的Aβ肽聚集的电化学研究,以及用电化学生物传感器检测生物液体中Aβ肽生物标志物的不同方法。
关键词: 阿尔茨海默病(AD),淀粉样β(Aβ)肽,伏安,纤维蛋白,聚集,吸附,氧化,AD生物标志物。
Current Medicinal Chemistry
Title:Electrochemistry of Alzheimer Disease Amyloid Beta Peptides
Volume: 25 Issue: 33
关键词: 阿尔茨海默病(AD),淀粉样β(Aβ)肽,伏安,纤维蛋白,聚集,吸附,氧化,AD生物标志物。
摘要: Alzheimer’s disease (AD) is a widespread form of dementia that is estimated to affect 44.4 million people worldwide. AD pathology is closely related to the accumulation of amyloid beta (Aβ) peptides in fibrils and plagues, the small oligomeric intermediate species formed during the Aβ peptides aggregation presenting the highest neurotoxicity.
This review discusses the recent advances on the Aβ peptides electrochemical characterization. The Aβ peptides oxidation at a glassy carbon electrode occurs in one or two steps, depending on the amino acid sequence, length and content. The first electron transfer reaction corresponds to the tyrosine Tyr10 amino acid residue oxidation, and the second to all three histidine (His6, His13 and His14) and one methionine (Met35) amino acid residues. The Aβ peptides aggregation and amyloid fibril formation are electrochemically detected via the electroactive amino acids oxidation peak currents decrease that occurs in a time dependent manner. The Aβ peptides redox behaviour is correlated with changes in the adsorption morphology from initially random coiled structures, corresponding to the Aβ peptide monomers in random coil or in α-helix conformations, to aggregates, protofibrils and two types of fibrils, corresponding to the Aβ peptides in a β-sheet configuration, observed by atomic force microscopy. Electrochemical studies of Aβ peptides aggregation, mediated by the interaction with metal ions, particularly zinc, copper and iron, and different methodologies concerning the detection of Aβ peptide biomarkers of AD in biological fluids, using electrochemical biosensors, are also discussed.
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Electrochemistry of Alzheimer Disease Amyloid Beta Peptides, Current Medicinal Chemistry 2018; 25 (33) . https://dx.doi.org/10.2174/0929867325666180214112536
DOI https://dx.doi.org/10.2174/0929867325666180214112536 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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