PTEN alpha is responsible for protection of brain against oxidative stress during aging

Article

关键词: MITOCHONDRIAL-DNA MUTATIONS;    MECHANISMS;    PHOSPHORYLATION;    INHIBITION;    HALLMARKS;    SYSTEM;    DEFECT;   

DOI  :  10.1096/fj.202100753R

来源: SCIE

【 摘 要 】

Neural cells are continuously subjected to oxidative stress arising from electrochemical activity, and cellular protection systems can turn on the oxidative stress response to detect and alleviate adverse conditions. However, the function and mechanism of the protective systems are complicated and remain largely elusive. We report that PTEN alpha, an isoform of the PTEN family, mediates defense signaling in response to oxidative stress during brain aging. We show that genetic ablation of Pten alpha in mice increases oxidative stress and results in neuronal cell death, culminating in accelerated decline of cognition and motor coordination as age increases. PTEN alpha maintains COX activity and promotes energy metabolism through abrogating NEDD4L-mediated degradation of COX4 in response to oxidative stress. In the presence of Parkinson's disease-associated mutation, PTEN alpha loses the capability to protect COX4 and ameliorate defects caused by Pten alpha deletion. Our study reveals an important role of PTEN alpha in response to oxidative stress. We propose that dysregulation of PTEN alpha signaling may accelerate the rate of brain aging and promote the development of neurodegenerative disorders.

【 授权许可】

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