Galzitskaya Oxana V, Surin Alexey K, Glyakina Anna V, Rogachevsky Vadim V, Selivanova Olga M
Institute of Protein Research, Russian Academy of Science, Pushchino, Moscow Region, Russia.
State Scientific Center of Applied Microbiology and Biotechnology, Moscow Region, Serpukhov District, Obolensk, Russia.
J Alzheimers Dis Rep. 2018 Oct 24;2(1):181-199. doi: 10.3233/ADR-180063.
Aβ and Aβ peptides are believed to be associated with Alzheimer's disease. Aggregates (plaques) of Aβ fibrils are found in the brains of humans affected with this disease. The mechanism of formation of Aβ fibrils has not been studied completely, which hinders the development of a correct strategy for therapeutic prevention of this neurodegenerative disorder. It has been found that the most toxic samples upon generation of fibrils are different oligomeric formations. Based on different research methods used for studying amyloidogenesis of Aβ and Aβ peptides and its amyloidogenic fragments, we have proposed a new mechanism of formation of amyloid fibrils. In accord with this mechanism, the main building unit for fibril generation is a ring-like oligomer. Association of ring-like oligomers results in the formation of fibrils of different morphologies. Our model implies that to prevent development of Alzheimer's disease a therapeutic intervention is required at the earliest stages of amyloidogenesis-at the stage of formation of ring-like oligomers. Therefore, the possibility of a personified approach for prevention not only of Alzheimer's disease development but also of other neurodegenerative diseases associated with the formation of fibrils is argued.
β淀粉样蛋白（Aβ）及其肽段被认为与阿尔茨海默病有关。在患此病的人类大脑中发现了Aβ纤维的聚集体（斑块）。Aβ纤维的形成机制尚未完全研究清楚，这阻碍了针对这种神经退行性疾病制定正确的治疗性预防策略。已发现，在纤维生成过程中，毒性最强的样本是不同的寡聚体形式。基于用于研究Aβ及其肽段的淀粉样蛋白生成及其淀粉样蛋白生成片段的不同研究方法，我们提出了一种新的淀粉样纤维形成机制。根据这一机制，纤维生成的主要构建单元是环状寡聚体。环状寡聚体的缔合导致形成不同形态的纤维。我们的模型表明，为预防阿尔茨海默病的发展，需要在淀粉样蛋白生成的最早阶段——环状寡聚体形成阶段进行治疗干预。因此，论证了采用个性化方法不仅预防阿尔茨海默病发展，还预防与纤维形成相关的其他神经退行性疾病的可能性。
