小分子蛋白酶体激动剂的研究进展

Research progress of small molecule proteasome activators

蛋白酶体控制着与生命活动密切相关蛋白的降解,对生物体内蛋白内稳态的维持起到了关键作用。随着衰老,体内蛋白酶体活性降低,导致一些受损蛋白的产生大于消耗,这些蛋白的堆积导致各种疾病的产生,如各种神经退行性疾病。因此,促进毒性蛋白降解被认为是治疗这类疾病的潜在方案,而提高蛋白酶体活性则是一种重要策略。但目前蛋白酶体激动剂的研究还处于初级阶段,本文将讨论目前各类小分子蛋白酶体激动剂的研究进展,包括研究方法、药理作用、构效关系和存在的问题等。

Proteasome controls the degradation of proteins closely related to life activities and plays a key role in the maintenance of protein homeostasis. Proteasome activities decrease with aging, followed by the overwhelming production of damaged proteins which far exceed the protein consumption. Accumulation of these proteins leads to various diseases including neurodegenerative diseases. Therefore, inducing toxic protein degradation is considered as a promising solution for the treatment of these diseases, while increasing the activity of proteasome is considered as an important strategy. However, the research in this field is still in the preliminary stage, and this review will focus on the discussion of the research progress of various small molecule proteasome activators, including research methods, pharmacological effects, structure-activity relationships and the existing problems.