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Inhibition of Amyloid Fibrillation by Small Molecules and Nanomaterials: Strategic Development of Pharmaceuticals Against Amyloidosis

机译:小分子和纳米材料抑制淀粉样蛋白纤维化:对淀粉样症的药物的战略发育

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摘要

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 Mark 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.
机译:淀粉样蛋白原纤维是一种特殊的自组装蛋白质分子,其在细胞中表现出各种毒性作用。不同的生理疾病,如Alzheimer,Parkinson,Huntington的疾病等,由于淀粉样蛋白形成和缺乏用于去除原纤维的适当细胞机制发生。因此,抑制淀粉样蛋白纤维化会发现巨大的应用,用于打击与淀粉样蛋白病相关的疾病。治疗淀粉样症状病的治疗方法绝对是挑战性,并且已经进行了许多策略来查找抗淀粉样蛋白分子。通过稳定天然构象或通过展开/错误的结构降低组装形成的可能性,可以通过稳定蛋白质的蛋白蛋白聚集的抑制来实现。各种小分子如天然存在的多酚,类黄酮,小有机分子,表面活性剂,染料,伴侣等已经证明了它们的能力来中断蛋白质的淀粉样蛋白纤维状。除此之外,在过去几年中,将不同的纳米材料进化为对标记淀粉样蛋白病的有效治疗抑制剂。部分展开的蛋白质分子与抑制剂之间的芳族和疏水相互作用被指向作为抑制的一般机制。在本文中,我们通过使用不同的小分子(天然和合成起源)以及纳米材料来提出抑制淀粉样蛋白病变的概述,用于对淀粉样疾病进行药物策略的制药策略。

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