Focusing on cyclin-dependent kinases 5: A potential target for neurological disorders

作者全名："Tian, Zhen; Feng, Bin; Wang, Xing-Qin; Tian, Jiao"

作者地址："[Tian, Zhen] Southwest Univ, Coll Pharmaceut Sci, Chongqing, Peoples R China; [Feng, Bin] Fourth Mil Med Univ, Natl Clin Res Ctr Oral Dis, Shaanxi Int Joint Res Ctr Oral Dis, Sch Stomatol,State Key Lab Mil Stomatol,Dept Pharm, Xian, Peoples R China; [Wang, Xing-Qin] Southern Med Univ, Nanfang Hosp, Dept Neurosurg, Guangzhou, Peoples R China; [Tian, Jiao] Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Minist Educ Key Lab Child Dev & Disorders, Childrens Hosp,Dept Infect,Chongqing Key Lab Child, Chongqing, Peoples R China"

通信作者："Tian, Z (通讯作者)，Southwest Univ, Coll Pharmaceut Sci, Chongqing, Peoples R China.; Tian, J (通讯作者)，Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Minist Educ Key Lab Child Dev & Disorders, Childrens Hosp,Dept Infect,Chongqing Key Lab Child, Chongqing, Peoples R China."

来源：FRONTIERS IN MOLECULAR NEUROSCIENCE

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:000889348600001

JCR分区：Q2

影响因子：4.8

年份：2022

卷号：15

期号：　

开始页：　

结束页：　

文献类型：Review

关键词：Cdk5; p35; neurological disorders; Parkinson's disease; Alzheimer's disease; stroke

摘要："Cyclin-dependent kinases 5 (Cdk5) is a special member of proline-directed serine threonine kinase family. Unlike other Cdks, Cdk5 is not directly involved in cell cycle regulation but plays important roles in nervous system functions. Under physiological conditions, the activity of Cdk5 is tightly controlled by p35 or p39, which are specific activators of Cdk5 and highly expressed in post-mitotic neurons. However, they will be cleaved into the corresponding truncated forms namely p25 and p29 under pathological conditions, such as neurodegenerative diseases and neurotoxic insults. The binding to truncated co-activators results in aberrant Cdk5 activity and contributes to the initiation and progression of multiple neurological disorders through affecting the down-stream targets. Although Cdk5 kinase activity is mainly regulated through combining with co-activators, it is not the only way. Post-translational modifications of Cdk5 including phosphorylation, S-nitrosylation, sumoylation, and acetylation can also affect its kinase activity and then participate in physiological and pathological processes of nervous system. In this review, we focus on the regulatory mechanisms of Cdk5 and its roles in a series of common neurological disorders such as neurodegenerative diseases, stroke, anxiety/depression, pathological pain and epilepsy."

基金机构：National Natural Science Foundation of China; Chongqing Natural Science Foundation; Science and Technology Research Project of Chongqing Education Commission; Fundamental Research Funds for the Central Universities; Guangdong Basic and Applied Basic Research Foundation; [81801329]; [cstc2021jcyj-msxmX0610]; [KJQN202100213]; [SWU-KQ22018]; [2020A1515110564]

基金资助正文："Funding Work in our laboratories was supported by National Natural Science Foundation of China (No. 81801329), Chongqing Natural Science Foundation (No. cstc2021jcyj-msxmX0610), Science and Technology Research Project of Chongqing Education Commission (No. KJQN202100213), Fundamental Research Funds for the Central Universities (No. SWU-KQ22018) to ZT, and Guangdong Basic and Applied Basic Research Foundation (No. 2020A1515110564) to X-QW."