Lazarev Vladimir F, Dutysheva Elizaveta A, Kanunikov Igor E, Guzhova Irina V, Margulis Boris A
Institute of Cytology of the Russian Academy of Sciences, 194064 Saint Petersburg, Russia.
Biological Faculty, St. Petersburg State University, 199034 Saint Petersburg, Russia.
Pharmaceuticals (Basel). 2023 Feb 16;16(2):312. doi: 10.3390/ph16020312.
The amyloid concept of Alzheimer's disease (AD) assumes the β-amyloid peptide (Aβ) as the main pathogenic factor, which injures neural and other brain cells, causing their malfunction and death. Although Aβ has been documented to exert its cytotoxic effect in a solitary manner, there is much evidence to claim that its toxicity can be modulated by other proteins. The list of such Aβ co-factors or interactors includes tau, APOE, transthyretin, and others. These molecules interact with the peptide and affect the ability of Aβ to form oligomers or aggregates, modulating its toxicity. Thus, the list of potential substances able to reduce the harmful effects of the peptide should include ones that can prevent the pathogenic interactions by specifically binding Aβ and/or its partners. In the present review, we discuss the data on Aβ-based complexes in AD pathogenesis and on the compounds directly targeting Aβ or the destructors of its complexes with other polypeptides.
阿尔茨海默病（AD）的淀粉样蛋白假说认为β-淀粉样肽（Aβ）是主要致病因素，它会损伤神经细胞和其他脑细胞，导致细胞功能异常和死亡。尽管已有文献证明Aβ可单独发挥细胞毒性作用，但有大量证据表明其毒性可受其他蛋白质调节。这类Aβ辅助因子或相互作用分子包括tau蛋白、载脂蛋白E（APOE）、转甲状腺素蛋白等。这些分子与该肽相互作用，影响Aβ形成寡聚体或聚集体的能力，从而调节其毒性。因此，能够降低该肽有害作用的潜在物质应包括那些可通过特异性结合Aβ和/或其伙伴来阻止致病相互作用的物质。在本综述中，我们讨论了AD发病机制中基于Aβ的复合物的数据，以及直接靶向Aβ或其与其他多肽复合物破坏剂的化合物。
