Abstract:

The spontaneous aggregation of β-amyloid (amyloid β-protein, Aβ) forms a large number of toxic oligomers, which lead to the death of neurons in the brain, thereby causing cognitive impairment, namely Alzheimer's disease (AD). Serious threat to human health. At present, lack of the understanding of the multiscale Aβ oligomers has seriously restricted the design and development of Aβ modulators or inhibitors. This review is devoted to introduction of the fundamentals of the on-pathway Aβ aggregation and the relationship with mesoscience, classification of the various mesoscale Aβ oligomers generated during Aβ assembly, and the cytotoxicity mediated by the Aβ oligomers. Then, the design strategies, inhibitory mechanisms, and functions of different modulators or inhibitors developed to date are discussed. Finally, major challenges on the development of Aβ-associated AD drugs are addressed and the future research into this crucial field is proposed.

Key words: Alzheimer's disease, amyloid β-protein, multiscale, aggregation, modulation, biomedical engineering

摘要：

β-淀粉样蛋白（amyloid β-protein，Aβ）的自发聚集形成大量毒性的寡聚体，导致脑内神经元死亡，从而引发认知障碍，即阿尔茨海默病（Alzheimer's disease，AD），严重威胁着人类的健康。Aβ聚集过程呈现复杂的多尺度自组装特性，目前尚缺乏对Aβ聚集过程多尺度寡聚体的认识，严重制约Aβ聚集抑制剂的设计开发。本文首先简述Aβ聚集的基本理论以及与介尺度科学的关系，分类介绍Aβ自组装过程中所产生的各种介尺度寡聚体及其介导的细胞毒性；之后归纳各种Aβ聚集抑制剂的设计策略、作用原理和作用效果；最后总结Aβ聚集及其调控研究中存在的主要挑战，并提出了进一步研究的重点方向。

关键词: 阿尔茨海默病, β-淀粉样蛋白, 多尺度, 聚集, 调控, 生物医学工程