Department of Neurology, The First Hospital of Lanzhou University, Lanzhou 730000, China.
College of Chemistry and Chemical Engineering, Hubei University, Wuhan 430062, China.
ACS Chem Neurosci. 2021 Nov 17;12(22):4236-4248. doi: 10.1021/acschemneuro.1c00544. Epub 2021 Nov 1.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by an imbalance between the production and clearance of amyloid-β (Aβ) species. AD not only influences the life quality of the patients but also heavily burdens the families and society. Therefore, it is an urgent mission to research and develop some new anti-amyloid aggregation drugs. In recent years, there were research and development of engineered nanostructures as Aβ amyloid inhibitors have attracted extensive attention and become a new frontier in nanomedicine. The effects of nanostructural surface properties (e.g., morphology, charge, hydrophobicity) on inhibition of Aβ aggregation are modulated by adsorbed Aβ peptides. Nevertheless, chirality has been seldom considered in recognition of Aβ species and modulation of Aβ aggregations. Moreover, a more relevant question for chiral inhibitors is little known about the molecular mechanism of how to interface chiral effects Aβ targeting recognition and effective mitigation of amyloidosis at the molecular level. Herein, we review recent experimental and theoretical results acquired in the specific areas of artificial chiral nanostructure inhibitors. This article will be essential to provide a microlevel insight into the effects of chiral nanointerfaces on amyloidosis processes as well as the development of chiral inhibitor drugs against Aβ fibrillation.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，其特征是淀粉样蛋白-β（Aβ）物质的产生和清除之间失衡。AD 不仅影响患者的生活质量，而且给家庭和社会带来沉重负担。因此，研究和开发一些新的抗淀粉样蛋白聚集药物是当务之急。近年来，作为 Aβ 淀粉样蛋白抑制剂的工程纳米结构的研发引起了广泛关注，成为纳米医学的新前沿。纳米结构表面性质（例如形态、电荷、疏水性）对 Aβ 聚集抑制的影响是通过吸附的 Aβ 肽来调节的。然而，在手性识别 Aβ 物种和调节 Aβ 聚集方面，手性很少被考虑。此外，对于手性抑制剂来说，一个更相关的问题是，对于手性如何在分子水平上靶向识别 Aβ 并有效减轻淀粉样变性，人们知之甚少。本文综述了在人工手性纳米结构抑制剂的特定领域中获得的最新实验和理论结果。本文将为深入了解手性纳米界面对淀粉样蛋白形成过程的影响以及针对 Aβ 纤维形成的手性抑制剂药物的开发提供重要依据。
