药学学报, 2022, 57(3): 605-614
引用本文:
余倩, 曹宇, 祝华建, 邵加安, 张建康. 小分子蛋白酶体激动剂的研究进展[J]. 药学学报, 2022, 57(3): 605-614.
YU Qian, CAO Yu, ZHU Hua-jian, SHAO Jia-an, ZHANG Jian-kang. Research progress of small molecule proteasome activators[J]. Acta Pharmaceutica Sinica, 2022, 57(3): 605-614.

小分子蛋白酶体激动剂的研究进展
余倩1,2, 曹宇1,2, 祝华建1,2, 邵加安1,2, 张建康1,2*
1. 浙大城市学院医学院, 浙江 杭州 310015;
2. 浙江大学药学院, 浙江 杭州 310058
摘要:
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。
关键词:    蛋白酶体      激动剂      构效关系      内在无序蛋白      神经退行性疾病     
Research progress of small molecule proteasome activators
YU Qian1,2, CAO Yu1,2, ZHU Hua-jian1,2, SHAO Jia-an1,2, ZHANG Jian-kang1,2*
1. School of Medicine, Zhejiang University City College, Hangzhou 310015, China;
2. College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
Abstract:
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.
Key words:    proteasome    activator    structure-activity relationship    intrinsically disordered protein    neurodegenerative disease   
收稿日期: 2021-10-28
DOI: 10.16438/j.0513-4870.2021-1549
基金项目: 国家自然科学基金资助项目(81803432);杭州市科技发展计划(20201203B150)。
通讯作者: 张建康,Tel:86-571-88016565,E-mail:zhang_jk@zucc.edu.cn
Email: zhang_jk@zucc.edu.cn
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