淀粉样蛋白沉积疾病与天然产物小分子关系的研究进展

Research progress of relations between amyloid deposition diseases and small molecules of natural products

淀粉样蛋白沉积疾病是错误折叠的蛋白在细胞内外聚集而引起的一类蛋白质构象类疾病。天然药物取材天然,来源广泛,作用平稳,毒副作用相对较小,是药物先导物的最佳来源之一。近年来我国传统中药的抗淀粉样蛋白沉积疾病的天然药物的发掘工作取得了一些成果。随着科技的进步和分离纯化手段的不断革新,天然产物小分子已成为发现和改造淀粉样蛋白沉积疾病药物的主要来源。该文回顾了在抗淀粉样蛋白沉积疾病天然产物小分子筛选和发掘工作中的一些进展,归纳了干预疾病的几个主要的介入点,包括抑制酶的作用、激活降解途径、稳定蛋白结构等,通过对淀粉样蛋白沉积疾病致病机制的深入了解和天然小分子研究进展的总结,以期为淀粉样蛋白沉积疾病的预防和治疗奠定基础。

Amyloid deposition diseases are a type of protein conformational diseases caused by the accumulation of misfolded proteins inside and outside cells.Natural medicines draw the materials from the nature,with a wide range of sources,stable effects and relatively small toxic and side effects.They are one of the best sources of drug lead material.In recent years,some achievements have been made in the discovery of natural drugs against amyloid disease based on traditional Chinese medicine.With the progress of science and technology and the continuous innovation of separation and purification methods,small molecules of natural products have become the main source of drugs for discovering and modifying amyloid deposition diseases.This article reviews some advances in the screening and discovery of small molecules of natural products against amyloid disease,and summarizes several major intervention points for interfering disease,including the inhibition of enzymes,activation of degradation pathways,stabilization of protein structure,etc.The deep understanding on the pathogenesis of amyloid diseases and summary of the research progress of natural small molecule will lay a foundation for the prevention and treatment of amyloid diseases.