Mitochondrial complex Ⅰ as a therapeutic target for Alzheimer’s disease

作     者：Eugenia Trushina Sergey Trushin Md Fayad Hasan Eugenia Trushina;Sergey Trushin;Md Fayad Hasan

作者机构：Department of NeurologyMayo ClinicRochesterMN 55905USA Department of Molecular Pharmacology and Experimental TherapeuticsMayo ClinicRochesterMN 55905USA 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2022年第12卷第2期

页      面：483-495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 grants from the National Institutes of Health [grant numbers RF1AG55549  R01NS107265  RO1AG062135  AG59093  AG072899  UG3/ UH3NS 113776  all to Eugenia Trushina  USA] 

主　　题：Mitochondria Mitochondria signaling ComplexⅠinhibitors Alzheimer’s disease Integrated stress response Neuroprotection Mitochondria targeted therapeutics Healthy aging 

摘      要：Alzheimer’s disease(AD),the most prominent form of dementia in the elderly,has no *** focused on the reduction of amyloid beta or hyperphosphorylated Tau protein have largely failed in clinical *** therapeutic targets and strategies are urgently *** data suggest that in response to environmental stress,mitochondria initiate an integrated stress response(ISR)shown to be beneficial for healthy aging and ***,we review data that implicate mitochondrial electron transport complexes involved in oxidative phosphorylation as a hub for small molecule-targeted therapeutics that could induce beneficial mitochondrial ***,partial inhibition of mitochondrial complex I has been exploited as a novel strategy for multiple human conditions,including AD,with several small molecules being tested in clinical *** discuss current understanding of the molecular mechanisms involved in this counterintuitive *** this strategy has also been shown to enhance health and life span,the development of safe and efficacious complex Ⅰ inhibitors could promote healthy aging,delaying the onset of age-related neurodegenerative diseases.