PINK1 kinase dysfunction triggers neurodegeneration in the primate brain without impacting mitochondrial homeostasis

作     者：Weili Yang Xiangyu Guo Zhuchi Tu Xiusheng Chen Rui Han Yanting Liu Sen Yan Qi Wang Zhifu Wang Xianxian Zhao Yunpeng Zhang Xin Xiong Huiming Yang Peng Yin Huida Wan Xingxing Chen Jifeng Guo Xiao-Xin Yan Lujian Liao Shihua Li Xiao-Jiang Li 

作者机构：Guangdong Key Laboratory of Non-human Primate ResearchGuangdong-Hongkong-Macao Institute of CNS RegenerationJinan UniversityGuangzhou 510632China Key Laboratory of Brain Functional Genomics of Ministry of EducationShanghai Key Laboratory of Brain Functional Genomicsand Shanghai Key Laboratory of Regulatory BiologySchool of Life SciencesEast China Normal UniversityShanghai 100021China Department of NeurologyXiangya HospitalCentral South UniversityChangsha 410008China Department of Anatomy and NeurobiologyXiangya School of MedicineCentral South UniversityChangsha 410008China 

出 版 物：《Protein & Cell》 (蛋白质与细胞（英文版）)

年 卷 期：2022年第13卷第1期

页      面：26-46页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 100204[医学-神经病学] 10[医学] 

基　　金：Guangdong Introducing Innovative and Entrepreneurial Teams, (2021ZT09Y007) Guangdong Key Laboratory of non-human primate research, (2020B121201006) Guangzhou Key Research Program on Brain Science, (202007030008) Yuanxi Biotech Inc National Natural Science Foundation of China, NSFC, (31872779, 32070534, 81830032, 81873736, 82071223, 82071421) Jinan University, JNU, (21620358) Fundamental Research Funds for the Central Universities National Key Research and Development Program of China Stem Cell and Translational Research, (2017YFA0105102, 2017YFA0105201) Special Project for Research and Development in Key areas of Guangdong Province, (2018B030337001) 

主　　题：Parkinson's disease neurogenesis neurodegeneration mitochondria non-human primates 

摘      要：In vitro studies have established the prevalent theory that the mitochondrial kinase PINK1 protects neurodegeneration by removing damaged mitochondria in Parkinson s disease(PD).However,difficulty in detecting endogenous PINK1 protein in rodent brains and cell lines has prevented the rigorous investigation of the in vivo role of *** we report that PINK1 kinase form is selectively expressed in the human and monkey ***/Cas9-mediated deficiency of PINK1 causes similar neurodegeneration in the brains of fetal and adult monkeys as well as cultured monkey neurons without affecting mitochondrial protein expression and ***,PINK1 mutations in the primate brain and human cells reduce protein phosphorylation that is important for neuronal function and *** findings suggest that PINK1 kinase activity rather than its mitochondrial function is essential for the neuronal survival in the primate brains and that its kinase dysfunction could be involved in the pathogenesis of PD.