Epigenetic Regulation of DAPK1 and Netrin-1 Drives Diabetic Encephalopathy.

ABSTRACT: Diabetic encephalopathy (DE) is a severe complication of diabetes characterized by cognitive impairment and synaptic dysfunction, while the underlying mechanisms are not clear. Here, a critical role is identified for death-associated protein kinase 1 (DAPK1) in DE pathogenesis using transgenic and streptozotocin-induced diabetic mouse models. Elevated DAPK1 expression in hippocampal excitatory neurons correlates with cognitive deficits, increases neuronal apoptosis, and disrupts synaptic plasticity. Conditional knockout of DAPK1 in CaMKII-positive neurons significantly mitigates these pathological features, improving cognitive performance and synaptic function. Mechanistically, it is demonstrated that reduced hippocampal microRNA (miR)-216a-5p levels in diabetic mice lead to DAPK1 upregula

SUBMITTER: Zhou Y 

PROVIDER: S-EPMC12499468 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature