The roles of RACK1 in the pathogenesis of Alzheimer's disease  

作　　者：Wenting He Xiuyu Shi Zhifang Dong 

机构地区：[1]Pediatric Research Institute,Ministry of Education Key Laboratory of Child Development and Disorders,National Clinical Research Center for Child Health and Disorders,Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders,Children's Hospital of Chongqing Medical University,Chongqing 400014,China

出　　处：《Journal of Biomedical Research》2024年第2期137-148,共12页生物医学研究杂志（英文版）

基　　金：supported by grants from the National Natural Science Foundation of China(Grant No.82071395);the Natural Science Foundation of Chongqing(Grant Nos.cstc2021ycjh-bgzxm0186,cstc2020jcyj-zdxmX0004,and cstc2021jcyj-bsh0023);the CQMU Program for Youth Innovation in Future Medicine(Grant No.W0044).

摘　　要：The receptor for activated C kinase 1(RACK1)is a protein that plays a crucial role in various signaling pathways and is involved in the pathogenesis of Alzheimer's disease(AD),a prevalent neurodegenerative disease.RACK1 is highly expressed in neuronal cells of the central nervous system and regulates the pathogenesis of AD.Specifically,RACK1 is involved in regulation of the amyloid-β precursor protein processing through α-or β-secretase by binding to different protein kinase C isoforms.Additionally,RACK1 promotes synaptogenesis and synaptic plasticity by inhibiting N-methyl-D-aspartate receptors and activating gamma-aminobutyric acid A receptors,thereby preventing neuronal excitotoxicity.RACK1 also assembles inflammasomes that are involved in various neuroinflammatory pathways,such as nuclear factor-kappa B,tumor necrosis factor-alpha,and NOD-like receptor family pyrin domain-containing 3 pathways.The potential to design therapeutics that block amyloid-β accumulation and inflammation or precisely regulate synaptic plasticity represents an attractive therapeutic strategy,in which RACK1 is a potential target.In this review,we summarize the contribution of RACK1 to the pathogenesis of AD and its potential as a therapeutic target.

关 键 词：RACK1 Alzheimer's disease PKC amyloid-β synaptic plasticity NEUROINFLAMMATION 

分 类 号：R749.16[医药卫生—神经病学与精神病学]