Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia.
Biochemistry (Mosc). 2023 Jan;88(Suppl 1):S75-S87. doi: 10.1134/S0006297923140055.
Progression of Alzheimer's disease is accompanied by the appearance of extracellular deposits in the brain tissues of patients with characteristic supramolecular morphology (amyloid plaques) the main components of which are β-amyloid isoforms (Aβ) and biometal ions (zinc, copper, iron). For nearly 40 years and up to the present time, the vast majority of experimental data indicate critical role of formation and accumulation of amyloid plaques (cerebral amyloidogenesis) in pathogenesis of Alzheimer's disease, however, nature of the molecular agents that initiate cerebral amyloidogenesis, as well as causes of aggregation of the native Aβ molecules in vivo remained unknown for a long time. This review discusses the current level of fundamental knowledge about the molecular mechanisms of interactions of zinc ions with a number of Aβ isoforms present in amyloid plaques of the patients with Alzheimer's disease, and also shows how this knowledge made it possible to identify driving forces of the cerebral amyloidogenesis in Alzheimer's disease and made it possible to determine fundamentally new biomarkers and drug targets as part of development of innovative strategy for diagnosis and treatment of Alzheimer's disease.
阿尔茨海默病的进展伴随着患者脑组织中出现具有特征性超分子形态的细胞外沉积物（淀粉样斑块），其主要成分是β-淀粉样蛋白异构体（Aβ）和生物金属离子（锌、铜、铁）。近 40 年来，直至目前，绝大多数实验数据表明淀粉样斑块的形成和积累（脑淀粉样形成）在阿尔茨海默病发病机制中的关键作用，然而，引发脑淀粉样形成的分子因素的本质，以及体内天然 Aβ分子聚集的原因在很长一段时间内都不得而知。这篇综述讨论了目前关于锌离子与存在于阿尔茨海默病患者淀粉样斑块中的几种 Aβ 异构体相互作用的分子机制的基本知识水平，并展示了这一知识如何能够确定阿尔茨海默病脑淀粉样形成的驱动力，并能够确定作为诊断和治疗阿尔茨海默病的创新策略的一部分的全新的生物标志物和药物靶点。
