KDM1A-mediated upregulation of METTL3 ameliorates Alzheimer's disease via enhancing autophagic clearance of p-Tau through m6A-dependent regulation of STUB1

Alzheimer's disease (AD) is a severe neurodegenerative disorder that progressively destroys cognitive skills. Exploring the mechanism underlying autophagic clearance of phosphorylated tau (p-Tau) contributes to developing novel therapeutic strategies for AD.SH-SY5Y and HT22 cells were treated with AβDysregulated levels of autophagy, p-Tau and m6A was observed in an in vitro model of AD. Overexpression of METTL3 or STUB1 enhanced autophagy but reduced p-Tau level in AβKDM1A-mediated upregulation of METTL3 enhances autophagic clearance of p-Tau through m6A-dependent regulation of STUB1, thus ameliorating Alzheimer's disease. Our study provides novel mechanistic insights into AD pathogenesis and potential drug targets for AD.