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.

错误折叠的和天然无序的球状蛋白质倾向于以交织的方式聚集在一起，形成纤维状蛋白质沉积物，称为淀粉样蛋白原纤维。这种不溶性原纤维的形成和沉积是称为淀粉样变性病的多种疾病的特征。已知其中一些蛋白质会导致人类多种退行性疾病，例如阿尔茨海默氏病（AD）的淀粉样β（Aβ），2型糖尿病的人胰岛淀粉样多肽（hIAPP，胰岛淀粉样多肽），α-突触核蛋白（α-syn ）帕金森氏病（PD）等。这些蛋白质在其天然状态下没有任何重要的序列或结构同源性，这一事实使疗法具有挑战性。然而，据观察，易于聚集的蛋白质和肽在原纤维形成过程中倾向于采用相似类型的二级结构。合理设计的肽可以是一种有效的抑制剂，已显示可通过特异性结合蛋白质中的淀粉样蛋白生成区域来破坏原纤维结构。下面的综述将分析基于序列的和基于结构的小肽的抑制能力，这些肽已显示出抑制蛋白质（例如Aβ，人胰岛淀粉样多肽和α-突触核蛋白）的淀粉样蛋白生成。