Sharma Vandna, Ghosh Kalyan Sundar
Department of Chemistry, National Institute of Technology, Hamirpur, Himachal Pradesh 177005, India.
Protein Pept Lett. 2019;26(5):315-323. doi: 10.2174/0929866526666190307164944.
Amyloid fibrils are a special class of self-assembled protein molecules, which exhibit various toxic effects in cells. Different physiological disorders such as Alzheimer's, Parkinson's, Huntington's diseases, etc. happen due to amyloid formation and lack of proper cellular mechanism for the removal of fibrils. Therefore, inhibition of amyloid fibrillation will find immense applications to combat the diseases associated with amyloidosis. The development of therapeutics against amyloidosis is definitely challenging and numerous strategies have been followed to find out anti-amyloidogenic molecules. Inhibition of amyloid aggregation of proteins can be achieved either by stabilizing the native conformation or by decreasing the chances of assembly formation by the unfolded/misfolded structures. Various small molecules such as naturally occurring polyphenols, flavonoids, small organic molecules, surfactants, dyes, chaperones, etc. have demonstrated their capability to interrupt the amyloid fibrillation of proteins. In addition to that, in last few years, different nanomaterials were evolved as effective therapeutic inhibitors against amyloidosis. Aromatic and hydrophobic interactions between the partially unfolded protein molecules and the inhibitors had been pointed as a general mechanism for inhibition. In this review article, we are presenting an overview on the inhibition of amyloidosis by using different small molecules (both natural and synthetic origin) as well as nanomaterials for development of pharmaceutical strategies against amyloid diseases.
淀粉样纤维是一类特殊的自组装蛋白质分子，在细胞中表现出多种毒性作用。诸如阿尔茨海默病、帕金森病、亨廷顿舞蹈症等不同的生理紊乱是由于淀粉样蛋白的形成以及缺乏清除纤维的适当细胞机制所致。因此，抑制淀粉样蛋白纤维化在对抗与淀粉样变性相关的疾病方面将有广泛应用。开发针对淀粉样变性的治疗方法无疑具有挑战性，人们已经采用了多种策略来寻找抗淀粉样生成分子。抑制蛋白质的淀粉样聚集可以通过稳定天然构象或减少未折叠/错误折叠结构形成聚集体的机会来实现。各种小分子，如天然存在的多酚、黄酮类化合物、小分子有机分子、表面活性剂、染料、伴侣蛋白等，已证明它们能够中断蛋白质的淀粉样纤维化。除此之外，在过去几年中，不同的纳米材料已发展成为对抗淀粉样变性的有效治疗抑制剂。部分未折叠的蛋白质分子与抑制剂之间的芳香族和疏水相互作用被认为是一种普遍的抑制机制。在这篇综述文章中，我们概述了使用不同的小分子（天然和合成来源）以及纳米材料抑制淀粉样变性，以开发针对淀粉样疾病的药物策略。
