A novel mechanism of PHB2-mediated mitophagy participating in the development of Parkinson's disease  

作　　者：Yongjiang Zhang Shiyi Yin Run Song Xiaoyi Lai Mengmeng Shen Jiannan Wu Junqiang Yan 

机构地区：[1]Key Laboratory of Neuromolecular Biology,The First Affiliated Hospital,College of Clinical Medicine of Henan University of Science and Technology,Luoyang,Henan Province,China [2]Department of Neurology,The First Affiliated Hospital,College of Clinical Medicine of Henan University of Science and Technology,Luoyang,Henan Province,China

出　　处：《Neural Regeneration Research》2024年第8期1828-1834,共7页中国神经再生研究（英文版）

基　　金：supported by the Key Science and Technology Research of Henan Province,No.222102310351(to JW);Luoyang 2022 Medical and Health Guiding Science and Technology Plan Project,No.2022057Y(to JY);Henan Medical Science and Technology Research Program Province-Ministry Co-sponsorship,No.SBGJ202002099(to JY)。

摘　　要：Endoplasmic reticulum stress and mitochondrial dysfunction play important roles in Parkinson s disease,but the regulato ry mechanism remains elusive.Prohibitin-2(PHB2)is a newly discove red autophagy receptor in the mitochondrial inner membrane,and its role in Parkinson’s disease remains unclear.Protein kinase R(PKR)-like endoplasmic reticulum kinase(PERK)is a factor that regulates cell fate during endoplasmic reticulum stress.Parkin is regulated by PERK and is a target of the unfolded protein response.It is unclear whether PERK regulates PHB2-mediated mitophagy thro ugh Parkin.In this study,we established a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced mouse model of Parkinson’s disease.We used adeno-associated virus to knockdown PHB2 expression.Our res ults showed that loss of dopaminergic neurons and motor deficits were aggravated in the MPTP-induced mouse model of Parkinson’s disease.Ove rexpression of PHB2 inhibited these abnormalities.We also established a 1-methyl-4-phenylpyridine(MPP+)-induced SH-SY5Y cell model of Parkinson’s disease.We found that ove rexpression of Parkin increased co-localization of PHB2 and microtubule-associated protein 1 light chain 3,and promoted mitophagy.In addition,MPP+regulated Parkin involvement in PHB2-mediated mitophagy through phosphorylation of PERK.These findings suggest that PHB2 participates in the development of Parkinson’s disease by intera cting with endoplasmic reticulum stress and Parkin.

关 键 词：endoplasmic reticulum dopaminergic neuron microtubule-associated protein 1 light chain 3 MITOPHAGY oxidative stress PARKIN Parkinson’s disease PKR-like endoplasmic reticulum kinase reactive oxygen species prohibitin-2 

分 类 号：R742.5[医药卫生—神经病学与精神病学]