Targeting autophagy using small-molecule compounds to improve potential therapy of Parkinson's disease.
Targeting autophagy using small-molecule compounds to improve potential therapy of Parkinson's disease.
复制标题
使用小分子化合物靶向自噬以改善帕金森病的潜在疗法
DOI：
10.1016/j.apsb.2021.02.016
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发表时间：
2021-10
期刊：
影响因子：
--
通讯作者：
Liu B
中科院分区：
文献类型：
--
作者：
Zhang K;Zhu S;Li J;Jiang T;Feng L;Pei J;Wang G;Ouyang L;Liu B
帕金森病（PD）是最普遍的神经退行性疾病之一，严重威胁着老年人的健康。目前的治疗已被证明可以缓解症状，并且发现新的小分子化合物已被视为一种有前途的策略。值得注意的是，自噬酶体通路（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，小分子化合物靶向自噬的药理学研究受到越来越多的关注。在本文中，我们将重点总结几个与自噬相关的靶点，如AMPK、mTORC1、ULK1、IMPase、LRRK2、beclin-1、TFEB、GCase、ERRα、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。本文就自噬在帕金森病（PD）发病中的作用机制作一综述。我们专注于几个细胞保护性自噬调节靶点，如LRRK2， C-Abelson, GCase， TFEB, ERRα, mTORC1， AMPK, ULK1， beclin-1和IMPase。同时列出了它们在PD模型中的相关小分子化合物。
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, ERRα, 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. In this review, we summarize the mechanism of autophagy in the pathogenesis of Parkinson's disease (PD). We focus on several cytoprotective autophagy-regulated targets, such as LRRK2, C-Abelson, GCase, TFEB, ERRα, mTORC1, AMPK, ULK1, beclin-1, and IMPase. At the meantime, their relevant small-molecule compounds in PD models are listed.
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