Fig. 2

Potential molecular mechanisms underlying DAPK1 dysregulation in AD. a Melatonin directly binds to the ankyrin repeats of DAPK1, promoting its ubiquitination and subsequent degradation in proteasomes. In AD, a downregulation of melatonin in the brain causes a reduction of proteasomal-degradation of DAPK1, leading to increased DAPK1 protein levels in the brain. b HSP90 is activated by Aβ accumulation in neurons. The activated HSP90 interacts with the kinase domain of DAPK1, resulting in the stabilization and activation of DAPK1 in the brain. c Some miRNAs (such as miR-143-3p and miR-191-5p) directly target the 3’ UTR of DAPK1 mRNA, leading to a translational repression of DAPK1 expression. In AD, the downregulation of these miRNAs may significantly promote the translation of DAPK1 mRNA, thereby elevating DAPK1 protein contents in the brain