LRRK2
疾病
帕金森病
激酶
富含亮氨酸重复
品脱1
突变
计算生物学
生物信息学
化学
基因
医学
生物
生物化学
帕金
内科学
作者
Tao Xu,Shuaishuai Xing,Mingkang Ma,Ziwei Xu,Qinghua Guan,Yuting Chen,Feng Feng,Wenyuan Liu,Tingkai Chen,Chen Yao,Haopeng Sun
标识
DOI:10.1021/acs.jmedchem.2c01552
摘要
Parkinson's disease (PD) is a progressive neurodegenerative disorder affecting millions of people worldwide. Mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2) are the most common genetic risk factor for PD. Elevated LRRK2 kinase activity is found in idiopathic and familial PD cases. LRRK2 mutations are involved in multiple PD pathogeneses, including dysregulation of mitochondrial homeostasis, ciliogenesis, etc. Here, we provide a comprehensive overview of the biological function, structure, and mutations of LRRK2. We also examine recent advances and challenges in developing LRRK2 inhibitors and address prospective protein-based targeting strategies. The binding mechanisms, structure-activity relationships, and pharmacokinetic features of inhibitors are emphasized to provide a comprehensive compendium on the rational design of LRRK2 inhibitors. We hope that this publication can serve as a guide for designing novel LRRK2 inhibitors based on the summarized facts and perspectives.
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