LRRK2
化学
小分子
富含亮氨酸重复
自噬
神经炎症
细胞生物学
激酶
帕金森病
药理学
神经科学
生物化学
生物
疾病
医学
病理
细胞凋亡
作者
Jiarui Hu,Dan Zhang,Keyue Tian,Changyu Ren,Heng Li,Congcong Lin,Xiaoli Huang,Jie Liu,Wuyu Mao,Jifa Zhang
标识
DOI:10.1016/j.ejmech.2023.115475
摘要
Leucine-rich repeat kinase 2 (LRRK2) is a multifunctional protein that orchestrates a diverse array of cellular processes, including vesicle transport, autophagy, lysosome degradation, neurotransmission, and mitochondrial activity. Hyperactivation of LRRK2 triggers vesicle transport dysfunction, neuroinflammation, accumulation of α-synuclein, mitochondrial dysfunction, and the loss of cilia, ultimately leading to Parkinson's disease (PD). Therefore, targeting LRRK2 protein is a promising therapeutic strategy for PD. The clinical translation of LRRK2 inhibitors was historically impeded by issues surrounding tissue specificity. Recent studies have identified LRRK2 inhibitors that have no effect on peripheral tissues. Currently, there are four small-molecule LRRK2 inhibitors undergoing clinical trials. This review provides a summary of the structure and biological functions of LRRK2, along with an overview of the binding modes and structure-activity relationships (SARs) of small-molecule inhibitors targeting LRRK2. It offers valuable references for developing novel drugs targeting LRRK2.
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