Zhang Kai, Zhu Shiou, Li Jiamei, Jiang Tingting, Feng Lu, Pei Junping, Wang Guan, Ouyang Liang, Liu Bo
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Collaborative Innovation Center of Biotherapy, Sichuan University, Chengdu 610041, China.
Innovation Center of Nursing Research, Nursing Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, China.
Acta Pharm Sin B. 2021 Oct;11(10):3015-3034. doi: 10.1016/j.apsb.2021.02.016. Epub 2021 Feb 26.
Parkinson's disease (PD), known as one of the most universal neurodegenerative diseases, is a serious threat to the health of the elderly. The current treatment has been demonstrated to relieve symptoms, and the discovery of new small-molecule compounds has been regarded as a promising strategy. Of note, the homeostasis of the autolysosome pathway (ALP) is closely associated with PD, and impaired autophagy may cause the death of neurons and thereby accelerating the progress of PD. Thus, pharmacological targeting autophagy with small-molecule compounds has been drawn a rising attention so far. In this review, we focus on summarizing several autophagy-associated targets, such as AMPK, mTORC1, ULK1, IMPase, LRRK2, beclin-1, TFEB, GCase, ERR, C-Abelson, and as well as their relevant small-molecule compounds in PD models, which will shed light on a clue on exploiting more potential targeted small-molecule drugs tracking PD treatment in the near future.
帕金森病（PD）是最常见的神经退行性疾病之一，对老年人的健康构成严重威胁。目前的治疗已被证明可缓解症状，发现新的小分子化合物被视为一种有前景的策略。值得注意的是，自噬溶酶体途径（ALP）的稳态与PD密切相关，自噬受损可能导致神经元死亡，从而加速PD的进展。因此，迄今为止，用小分子化合物对自噬进行药理学靶向已引起越来越多的关注。在这篇综述中，我们着重总结了几个与自噬相关的靶点，如AMPK、mTORC1、ULK1、IMPase、LRRK2、beclin-1、TFEB、GCase、ERR、C-Abelson，以及它们在PD模型中的相关小分子化合物，这将为在不久的将来开发更多潜在的靶向小分子药物追踪PD治疗提供线索。
