Department of Biotechnology and Biosciences, University of Milano Bicocca, 20126 Milano, Italy.
Curr Med Chem. 2010;17(27):2990-3006. doi: 10.2174/092986710791959729.
The progressive production and subsequent accumulation of β-amyloid (Aβ), a proteolytic fragment of the membrane-associated amyloid precursor protein (APP), plays a central role in Alzheimer's Disease (AD). Aβ is released in a soluble form that may be responsible for cognitive dysfunction in the early stages of the disease, then progressively forms oligomeric, multimeric and fibrillar aggregates, triggering neurodegeneration. Eventually, the aggregation and accumulation of Aβ culminates with the formation of extracellular plaques, one of the morphological hallmarks of the disease, detectable post-mortem in AD brains. In this review we report the known structural features of amyloid peptides and fibrils, and we give an overview of all small molecules that have been found to interact with Aβ aggregation. Deeper knowledge of the mechanism leading to amyloid fibrils along with their molecular structure and the molecular interactions responsible for activity of small molecules could supply useful information for the design of new AD therapeutic agents.
β-淀粉样蛋白（Aβ）是膜相关淀粉样前体蛋白（APP）的蛋白水解片段，其渐进性产生和随后的积累在阿尔茨海默病（AD）中起着核心作用。Aβ以可溶性形式释放，可能是疾病早期认知功能障碍的原因，然后逐渐形成寡聚体、多聚体和纤维状聚集物，引发神经退行性变。最终，Aβ的聚集和积累导致细胞外斑块的形成，这是该疾病的形态学标志之一，在 AD 大脑中死后可检测到。在这篇综述中，我们报告了已知的淀粉样肽和纤维的结构特征，并概述了所有已发现与 Aβ聚集相互作用的小分子。对导致淀粉样纤维形成的机制以及它们的分子结构和小分子活性的分子相互作用有更深入的了解，可以为设计新的 AD 治疗药物提供有用的信息。
