泛素-蛋白酶体系统、自噬-溶酶体系统与代谢性疾病

Ubiquitin-proteasomal system,autophagy-lysosomal system and metabolic diseases

泛素-蛋白酶系统(ubiquitin-protease system,UPS)和自噬-溶酶体系统(autophagy-lysosomal system,ALS)是两种清理系统,负责清除功能失调/错误折叠的蛋白质,从而充当真核细胞中蛋白质稳态的关键调节因子。代谢性疾病是全球性的健康挑战,研究其病理生理机制是从根本上解决该类疾病的关键。在代谢性疾病中,由于UPS、ALS功能障碍而导致蛋白质稳态丧失,从而引起受损蛋白质过分累积是引起机体代谢功能障碍的重要原因之一。因此,本文重点阐述了UPS和ALS的基本过程及两者相互调控的机制,为开发新的药物作用靶点及研发新药物开辟新的途径。

The ubiquitin-protease system(UPS)and autophagy-lysosomal system(ALS)are two clearance systems which are responsible for eliminating dysfunctional/misfolded proteins,thus acting as critical regulators of protein homeostasis within eukaryotic cells.Metabolic diseases represent a global health challenge,and understanding their pathophysiological mechanisms is the key to addressing the root causes of these diseases.In metabolic diseases,the loss of protein homeostasis due to the dysfunction of UPS and ALS,results in excessive accumulation of damaged proteins,is one of the significant contributing factors to impaired metabolic functions within organisms.Consequently,this paper focuses on elucidating the basic processes of UPS and ALS,as well as the mechanism by which they mutually regulate,which gives a new insight to the targets and the development of new drugs.