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

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

(2024) 13:4 | Tao Zhang, Byeong Mo Kim, Tae Ho Lee
Alzheimer's disease (AD) is a prevalent form of dementia characterized by neurofibrillary tangles, senile plaques, brain atrophy, and synaptic dysfunctions. Death-associated protein kinase 1 (DAPK1) is a serine/threonine kinase widely expressed in the central nervous system, and its dysregulation has been linked to various neurological diseases, including AD. This review discusses the role of DAPK1 in AD, focusing on its involvement in tau hyperphosphorylation, amyloid-β (Aβ) deposition, neuronal cell death, and synaptic degeneration. DAPK1 dysregulation is associated with increased Aβ production, tau hyperphosphorylation, and neuronal apoptosis. The review also explores the molecular mechanisms underlying DAPK1 dysregulation in AD, including post-transcriptional regulation by miRNAs and protein stability modulation by chaperones. Additionally, it highlights the potential of DAPK1 as a therapeutic target for AD, discussing recent progress in developing DAPK1 modulators and their applications in AD intervention. The findings suggest that DAPK1 may serve as a multifunctional therapeutic target for the development of disease-modifying treatments for AD and other neurological disorders.Alzheimer's disease (AD) is a prevalent form of dementia characterized by neurofibrillary tangles, senile plaques, brain atrophy, and synaptic dysfunctions. Death-associated protein kinase 1 (DAPK1) is a serine/threonine kinase widely expressed in the central nervous system, and its dysregulation has been linked to various neurological diseases, including AD. This review discusses the role of DAPK1 in AD, focusing on its involvement in tau hyperphosphorylation, amyloid-β (Aβ) deposition, neuronal cell death, and synaptic degeneration. DAPK1 dysregulation is associated with increased Aβ production, tau hyperphosphorylation, and neuronal apoptosis. The review also explores the molecular mechanisms underlying DAPK1 dysregulation in AD, including post-transcriptional regulation by miRNAs and protein stability modulation by chaperones. Additionally, it highlights the potential of DAPK1 as a therapeutic target for AD, discussing recent progress in developing DAPK1 modulators and their applications in AD intervention. The findings suggest that DAPK1 may serve as a multifunctional therapeutic target for the development of disease-modifying treatments for AD and other neurological disorders.
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