Phosphorylated tau as a toxic agent in synaptic mitochondria: implications in aging and Alzheimer’s disease

作     者：Angie K.Torres Bastián I.Rivera Catalina M.Polanco Claudia Jara Cheril Tapia-Rojas Angie K.Torres;Bastián I.Rivera;Catalina M.Polanco;Claudia Jara;Cheril Tapia-Rojas

作者机构：Laboratory of Neurobiology of AgingCentro de Biología Celular y Biomedicina(CEBICEM)Facultad de Medicina y CienciaUniversidad San SebastiánSede Los LeonesSantiagoChile 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2022年第17卷第8期

页      面：1645-1651页

核心收录：

学科分类：1002[医学-临床医学] 100203[医学-老年医学] 10[医学] 

基　　金：supported by FONDECYT,No.11170546,CONICYT PAI,No.77170091(to CTR) FONDECYT,No.3210591(to CJ) 

主　　题：age pathology aging Alzheimer’s disease hippocampus memory mitochondria PHF-1 phosphorylated tau synaptic mitochondria tau 

摘      要：During normal aging,there is a decline in all physiological functions in the *** of the most affected organs is the brain,where neurons lose their proper synaptic function leading to cognitive *** is one of the main risk factors for the development of neurodegenerative diseases,such as Alzheimer’s *** of the main responsible factors for synaptic dysfunction in aging and neurodegenerative diseases is the accumulation of abnormal proteins forming *** most studied brain aggregates are the senile plaques,formed by Aβpeptide;however,the aggregates formed by phosphorylated tau protein have gained relevance in the last years by their *** is reported that neurons undergo severe mitochondrial dysfunction with age,with a decrease in adenosine 5′-triphosphate production,loss of the mitochondrial membrane potential,redox imbalance,impaired mitophagy,and loss of calcium buffer ***,abnormal tau protein interacts with several mitochondrial proteins,suggesting that it could induce mitochondrial ***,whether tau-mediated mitochondrial dysfunction occurs indirectly or directly is still unknown.A recent study of our laboratory shows that phosphorylated tau at Ser396/404(known as PHF-1),an epitope commonly related to pathology,accumulates inside mitochondria during normal *** accumulation occurs preferentially in synaptic mitochondria,which suggests that it may contribute to the synaptic failure and cognitive impairment seen in aged ***,we review the main tau modifications promoting mitochondrial dysfunction,and the possible mechanism ***,we discuss the evidence that supports the possibility that phosphorylated tau accumulation in synaptic mitochondria promotes synaptic and cognitive impairment in ***,we show evidence and argue about the presence of phosphorylated tau PHF-1 inside mitochondria in Alzheimer’s disease,which could be considered as an early event