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作 者:Xiu-Sheng Chen Rui Han Yan-Ting Liu Wei Huang Qi Wang Xin Xiong Ying Zhang Jian-Guo Zhao Shi-Hua Li Xiao-Jiang Li Wei-Li Yang
机构地区:[1]Guangdong Key Laboratory of Non-human Primate Research,Key Laboratory of CNS Regeneration(Ministry of Education),GHM Institute of CNS Regeneration,Jinan University,Guangzhou,Guangdong 510632,China [2]State Key Laboratory of Stem Cell and Reproductive Biology,Institute of Zoology,Chinese Academy of Sciences,Beijing 100101,China [3]Beijing Institute for Stem Cell and Regenerative Medicine,Beijing 100101,China [4]University of Chinese Academy of Sciences,Beijing 100049,China
出 处:《Zoological Research》2024年第2期242-252,共11页动物学研究(英文)
基 金:supported by the National Natural Science Foundation of China (32070534,32370567,82371874,81830032,31872779,82071421,81873736);Key Field Research and Development Program of Guangdong Province (2018B030337001);Guangzhou Key Research Program on Brain Science (202007030008);Department of Science and Technology of Guangdong Province (2021ZT09Y007,2020B121201006);Guangdong Basic and Applied Basic Research Foundation (2023B1515020031,2022A1515012301);Fundamental Research Funds for the Central Universities (Jinan University,21620358)。
摘 要:PTEN-induced putative kinase 1(PINK1),a mitochondrial kinase that phosphorylates Parkin and other proteins,plays a crucial role in mitophagy and protection against neurodegeneration.Mutations in PINK1 and Parkin can lead to loss of function and early onset Parkinson's disease.However,there is a lack of strong in vivo evidence in rodent models to support the theory that loss of PINK1 affects mitophagy and induces neurodegeneration.Additionally,PINK1 knockout pigs(Sus scrofa)do not appear to exhibit neurodegeneration.In our recent work involving non-human primates,we found that PINK1 is selectively expressed in primate brains,while absent in rodent brains.To extend this to other species,we used multiple antibodies to examine the expression of PINK1 in pig tissues.In contrast to tissues from cynomolgus monkeys(Macaca fascicularis),our data did not convincingly demonstrate detectable PINK1expression in pig tissues.Knockdown of PINK1 in cultured pig cells did not result in altered Parkin and BAD phosphorylation,as observed in cultured monkey cells.A comparison of monkey and pig striatum revealed more PINK1-phosphorylated substrates in the monkey brain.Consistently,PINK1 knockout in pigs did not lead to obvious changes in the phosphorylation of Parkin and BAD.These findings provide new evidence that PINK1expression is specific to primates,underscoring the importance of non-human primates in investigating PINK1function and pathology related to PINK1 deficiency.
关 键 词:PINK1 PARKIN MITOCHONDRIA PHOSPHORYLATION Non-human primates PIGS
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