Targeting whole body metabolism and mitochondrial bioenergetics in the drug development for Alzheimer’s disease  

作　　者：Steven N.Austad Scott Ballinger Thomas W.Buford Christy S.Carter Daniel L.Smith Jr Victor Darley-Usmar Jianhua Zhang 

机构地区：[1]Department of Biology,University of Alabama at Birmingham,Birmingham,AL 35294,USA [2]Department of Pathology,University of Alabama at Birmingham,Birmingham,AL 35294,USA [3]Department of Medicine,University of Alabama at Birmingham,Birmingham,AL 35294,USA [4]Department of Nutrition Sciences,University of Alabama at Birmingham,Birmingham,AL 35294,USA

出　　处：《Acta Pharmaceutica Sinica B》2022年第2期511-531,共21页药学学报（英文版）

基　　金：the UAB NSC P30 AG05886(SA,SB,TB,CC,DLS,VDU,JZ)for partial support。

摘　　要：Aging is by far the most prominent risk factor for Alzheimer’s disease(AD),and both aging and AD are associated with apparent metabolic alterations.As developing effective therapeutic interventions to treat AD is clearly in urgent need,the impact of modulating whole-body and intracellular metabolism in preclinical models and in human patients,on disease pathogenesis,have been explored.There is also an increasing awareness of differential risk and potential targeting strategies related to biological sex,microbiome,and circadian regulation.As a major part of intracellular metabolism,mitochondrial bioenergetics,mitochondrial quality-control mechanisms,and mitochondria-linked inflammatory responses have been considered for AD therapeutic interventions.This review summarizes and highlights these efforts.

关 键 词：Mitochondrial DNA Mitochondrial electron transport chain Mitochondrial quality control Reactive species DAMPS Hexokinase biosynthesis pathway Diabetes Circadian regulation MICROBIOME 

分 类 号：R749.16[医药卫生—神经病学与精神病学]