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한빛사논문
- 조회236
Transl. Neurodegener., Jan 09 2024, 13 (1) 4 | https://doi.org/10.1186/s40035-023-00395-5
Death-associated protein kinase 1 as a therapeutic target for Alzheimer's disease
Tao Zhang1, Byeong Mo Kim2* and Tae Ho Lee1*
1Fujian 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
2Research Center for New Drug Development, AgingTarget Inc., 10F Ace Cheonggye Tower, 53, Seonggogae-Ro, Uiwang-Si 16006, Gyeonggi-Do, Korea
*Correspondence: Byeong Mo Kim, Tae Ho Lee
Abstract
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 Aβ and 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, Aβ deposition, 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.
논문정보
- Review Paper
- 2024년 01월 (BRIC 등록일 2024-01-12)
- 국내(교신)+국외 연구진
- 의약학 > 신경의학
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