Department of Biotechnology and Medical Engineering, National Institute of Technology Rourkela, Rourkela, 769008, Odisha, India.
Department of Biotechnology and Medical Engineering, National Institute of Technology Rourkela, Rourkela, 769008, Odisha, India.
Arch Biochem Biophys. 2020 Nov 30;695:108614. doi: 10.1016/j.abb.2020.108614. Epub 2020 Sep 30.
Misfolded and natively disordered globular proteins tend to aggregate together in an interwoven fashion to form fibrous, proteinaceous deposits referred to as amyloid fibrils. Formation and deposition of such insoluble fibrils are the characteristic features of a broad group of diseases, known as amyloidosis. Some of these proteins are known to cause several degenerative disorders in humans, such as Amyloid-Beta (Aβ) in Alzheimer's disease (AD), human Islet Amyloid Polypeptide (hIAPP, amylin) in type 2 diabetes, α-synuclein (α-syn) in Parkinson's disease (PD) and so on. The fact that these proteins do not share any significant sequence or structural homology in their native states make therapy quite challenging. However, it is observed that aggregation-prone proteins and peptides tend to adopt a similar type of secondary structure during the formation of fibrils. Rationally designed peptides can be a potent inhibitor that has been shown to disrupt the fibril structure by binding specifically to the amyloidogenic region(s) within a protein. The following review will analyze the inhibitory potency of both sequence-based and structure-based small peptides that have been shown to inhibit amyloidogenesis of proteins such as Aβ, human amylin, and α-synuclein.
错误折叠和天然无序的球状蛋白质往往以交织的方式聚集在一起，形成纤维状的蛋白质沉积物，称为淀粉样纤维。这种不溶性纤维的形成和沉积是一大类疾病的特征，称为淀粉样变性。这些蛋白质中的一些已知会导致人类的几种退行性疾病，如阿尔茨海默病（AD）中的淀粉样-β（Aβ）、2 型糖尿病中的人胰岛淀粉样多肽（hIAPP，胰岛淀粉样肽）、帕金森病（PD）中的α-突触核蛋白（α-syn）等。这些蛋白质在天然状态下没有任何显著的序列或结构同源性，这使得治疗变得极具挑战性。然而，人们观察到，易于聚集的蛋白质和肽在形成纤维时往往采用类似的二级结构。经过合理设计的肽可以作为一种有效的抑制剂，通过特异性结合蛋白质中的淀粉样形成区域来破坏纤维结构。本文综述分析了已被证明可抑制 Aβ、人胰岛淀粉样肽和 α-突触核蛋白等蛋白质淀粉样生成的基于序列和基于结构的小肽的抑制效力。
