Death-Associated Protein Kinase 1 (DAPK1) Signalling at the Crossroads of Apoptosis, Autophagy, and Post-transcriptional Cascades in Neurodegenerative Diseases
Review uncovers the multifaceted pathogenic roles of DAPK1 in neurodegenerative diseases, highlighting its viability as a target for neuroprotective therapies.
Key Points
Synthesize structural, regulatory, and signaling mechanisms of DAPK1 in neuronal cell death and evaluate therapeutic strategies targeting DAPK1 across acute and chronic neurodegenerative disorders.
Reviewed molecular mechanisms controlling DAPK1 expression and activity, including transcriptional, post-transcriptional (microRNAs), and post-translational pathways.
Examined DAPK1-mediated pathology across Alzheimer's disease, Parkinson's disease, Huntington's disease, diabetic encephalopathy, traumatic brain injury, and ischemic stroke.
Assessed pharmacological strategies targeting DAPK1, including kinase inhibitors, competitive peptides, and gene-regulatory approaches, alongside translational challenges.
DAPK1 overactivation drives neuronal injury via NMDA receptor-mediated excitotoxicity, tau and α-synuclein hyperphosphorylation, autophagic dysregulation, synaptic loss, and apoptotic cascades.
DAPK1 is tightly modulated by complex regulatory networks including transcription factors, specific microRNAs, phosphorylation switches, and targeted protein degradation.
Targeting DAPK1 with small molecules or peptides presents strong neuroprotective potential, though selective inhibition and blood–brain barrier penetration remain key hurdles.