文献类型：期刊文献

英文题名：Recent advances in targeting leucine-rich repeat kinase 2 as a potential strategy for the treatment of Parkinson's disease

作者：Cao, Ruiwei[1,3];Chen, Caiping[1,3];Wen, Jing[3];Zhao, Weihe[3];Zhang, Chaojun[3];Sun, Longhui[3];Yuan, Liyan[3];Wu, Chunlei[1,2];Shan, Lei[1];Xi, Meiyang[1,2];Sun, Haopeng[4]

机构：[1]Shaoxing Univ, Zhejiang Engn Res Ctr Fat Soluble Vitamin, Shaoxing 312000, Peoples R China;[2]Shaoxing Univ, Coll Chem & Chem Engn, Shaoxing 312000, Peoples R China;[3]Zhejiang Med Co Ltd, Shaoxing 312500, Peoples R China;[4]China Pharmaceut Univ, Dept Med Chem, Nanjing 210009, Peoples R China

年份：2023

卷号：141

外文期刊名：BIOORGANIC CHEMISTRY

收录：SCI-EXPANDED(收录号：WOS:001092920200001)、、Scopus(收录号：2-s2.0-85173869007)、WOS

基金：Acknowledgments The authors greatly acknowledge the support from the National Natural Science Foundation of China (No. 22278270) , Natural Science Foundation of Zhejiang Province (No. LGG21E050009) and Science and Technology Research Projects of Keqiao District of Shaoxing City (No. 2022JBGS303) .

语种：英文

外文关键词：Parkinson 's disease (PD); Mutations; Leucine-rich repeat kinase 2 (LRRK2) inhibitors

外文摘要：Parkinson's disease (PD) is the second most common neurodegenerative disease. Several single gene mutations involved in PD have been identified such as leucine-rich repeat kinase 2 (LRRK2), the most common cause of sporadic and familial PD. Its mutations have attracted much attention to therapeutically targeting this kinase. To date, many compounds including small chemical molecules with diverse scaffolds and RNA agents have been developed with significant amelioration in preclinical PD models. Currently, five candidates, DNL201, DNL151, WXWH0226, NEU-723 and BIIB094, have advanced to clinical trials for PD treatment. In this review, we describe the structure, pathogenic mutations and the mechanism of LRRK2, and summarize the development of LRRK2 inhibitors in preclinical and clinical studies, trying to provide an insight into targeting LRRK2 for PD intervention in future.