Phosphoinositide-3-kinase regulatory subunit 4 participates in the occurrence and development of amyotrophic lateral sclerosis by regulating autophagy  

作　　者：Yue Liu Cai-Hui Wei Cheng Li Wen-Zhi Chen Yu Zhu Ren-Shi Xu 

机构地区：[1]Department of Neurology,First Affiliated Hospital of Nanchang Medical College,Jiangxi Provincial People’s Hospital,Affiliated People’s Hospital of Nanchang University,Nanchang,Jiangxi Province,China

出　　处：《Neural Regeneration Research》2022年第7期1609-1616,共8页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China(Nos.30560042,81160161 and 81360198);Education Department of Jiangxi Province(No.GJJ170021);Jiangxi Provincial Department of Science and Technology(Nos.[2014]-47,20142BBG70062,20171BAB215022,20192BAB205043);Health Commission of Jiangxi Province(No.20181019)(all to RSX)。

摘　　要：The development of amyotrophic lateral sclerosis(ALS)may be related to the abnormal alterations of multiple proteins.Our previous study revealed that the expression of phosphoinositide-3-kinase regulatory subunit 4(PIK3R4)was decreased in ALS.However,the role of PIK3R4 in ALS pathogenesis remains unknown.This study was the first to find that transfection of PC12 cells with small interfering RNA against the PIK3R4 gene significantly decreased the expression levels of PIK3R4 and the autophagy-related proteins p62 and LC3.Additionally,in vivo experiments revealed that the PIK3R4 protein was extensively expressed in the anterior horn,posterior horn,central canal,and areas surrounding the central canal in cervical,thoracic,and lumbar segments of the spinal cord in adult mice.PIK3R4 protein was mainly expressed in the neurons within the spinal lumbar segments.PIK3R4 and p62 expression levels were significantly decreased at both the pre-onset and onset stages of ALS disease in Tg(SOD1*G93A)1 Gur mice compared with control mice,but these proteins were markedly increased at the progression stage.LC3 protein expression did not change during progression of ALS.These findings suggest that PIK3R4 likely participates in the prevention of ALS progression.This study was approved by the Ethics Committee for Animal Care and Use of Jiangxi Provincial People’s Hospital,Affiliated People’s Hospital of Nanchang University(approval No.2020025)on March 26,2020.

关 键 词：amyotrophic lateral sclerosis AUTOPHAGY LC3 p62 PC12 cell phosphoinositide-3-kinase regulatory subunit 4 spinal cord Tg(SOD1*G93A)1Gur mice 

分 类 号：R456[医药卫生—治疗学] R741[医药卫生—临床医学]