Novel insights into the mechanism of reactive oxygen species-mediated neurodegeneration  

作　　者：Shuji Wakatsuki Toshiyuki Araki 

机构地区：[1]Department of Peripheral Nervous System Research,National Institute of Neuroscience,National Center of Neurology and Psychiatry,Tokyo,Japan

出　　处：《Neural Regeneration Research》2023年第4期746-749,共4页中国神经再生研究（英文版）

摘　　要：Neurite degeneration,a major component of many neurodegenerative diseases,such as Parkinson’s disease,Alzheimer’s disease,and amyotrophic lateral sclerosis,is not part of the typical apoptosis signaling mechanism,but rather it appears that a self-destructive process is in action.Oxidative stress is a well-known inducer of neurodegenerative pathways:neuronal cell death and neurite degeneration.Although oxidative stress exerts cytotoxic effects leading to neuronal loss,the pathogenic mechanisms and precise signaling pathways by which oxidative stress causes neurite degeneration have remained entirely unknown.We previously reported that reactive oxygen species generated by NADPH oxidases induce activation of the E3 ubiquitin ligase ZNRF1 in neurons,which promotes neurite degeneration.In this process,the phosphorylation of an NADPH oxidase subunit p47-phox at the 345serine residue serves as an important checkpoint to initiate the ZNRF1-dependent neurite degeneration.Evidence provides new insights into the mechanism of reactive oxygen species-mediated neurodegeneration.In this review,we focus specifically on reactive oxygen species-induced neurite degeneration by highlighting a phosphorylation-dependent regulation of the molecular interaction between ZNRF1 and the NADPH oxidase complex.

关 键 词：neurite degeneration oxidative stress PHOSPHORYLATION reactive oxygen species ubiquitin ligase 

分 类 号：R741[医药卫生—神经病学与精神病学]