Death-associated protein kinase 1 as a therapeutic target for Alzheimer’s disease  

作　　者：Tao Zhang Byeong Mo Kim Tae Ho Lee 

机构地区：[1]Fujian Key Laboratory of Translational Research in Cancer and Neurodegenerative Diseases,Institute of Basic Medicine,School of Basic Medical Sciences,Fujian Medical University,1 Xuefu North Road,Fuzhou 350122,Fujian,China [2]Research Center for New Drug Development,AgingTarget Inc.,10F Ace Cheonggye Tower,53,Seonggogae-Ro,Uiwang-Si 16006,Gyeonggi-Do,Korea

出　　处：《Translational Neurodegeneration》2024年第1期1038-1063,共26页转化神经变性病(英文)

基　　金：supported by the National Natural Science Foundation of China(82271449 and 81970993)to T.H.Lee;T.Zhang receives financial support from the National Natural Science Foundation of China(82001128);the Natural Science Foundation of Fujian Province(2021J01672).

摘　　要：Alzheimer’s disease(AD)is the most prevalent form of dementia in the elderly and represents a major clinical challenge in the ageing society.Neuropathological hallmarks of AD include neurofibrillary tangles composed of hyperphosphorylated tau,senile plaques derived from the deposition of amyloid-β(Aβ)peptides,brain atrophy induced by neuronal loss,and synaptic dysfunctions.Death-associated protein kinase 1(DAPK1)is ubiquitously expressed in the central nervous system.Dysregulation of DAPK1 has been shown to contribute to various neurological diseases including AD,ischemic stroke and Parkinson’s disease(PD).We have established an upstream effect of DAPK1 on Aβand tau pathologies and neuronal apoptosis through kinase-mediated protein phosphorylation,supporting a causal role of DAPK1 in the pathophysiology of AD.In this review,we summarize current knowledge about how DAPK1 is involved in various AD pathological changes including tau hyperphosphorylation,Aβdeposition,neuronal cell death and synaptic degeneration.The underlying molecular mechanisms of DAPK1 dysregulation in AD are discussed.We also review the recent progress regarding the development of novel DAPK1 modulators and their potential applications in AD intervention.These findings substantiate DAPK1 as a novel therapeutic target for the development of multifunctional disease-modifying treatments for AD and other neurological disorders.

关 键 词：Death-associated protein kinase 1 Alzheimer’s disease TAU Amyloid-β Neuronal cell death Therapeutic target 

分 类 号：R749.16[医药卫生—神经病学与精神病学]