Tau accumulation triggers STAT1-dependent memory deficits by suppressing NMDA receptor expression

ABSTRACT: Intracellular tau accumulation forming neurofibrillary tangles is one hallmark of Alzheimer's disease (AD), but how tau accumulation induces synaptic impairment remains elusive. Here, by overexpressing human full-length wildtype tau (hTau) to mimic tau abnormalities as seen in the brain of sporadic AD patients, we find that hTau accumulation activates JAK2-dependent STAT1 phosphorylation at Tyr701, triggering STAT1 dimerization, activation and nuclear translocation. STAT1 activation subsequently suppresses the expression of N-methyl-D-aspartate receptors (NMDARs) through direct binding to specific GAS elements in the GluN1, GluN2A and GluN2B promoters. Knockdown of STAT1, or the expression of dominant negative Y701F-STAT1 in mice, efficiently rescues hTau-induced suppression of NMDAR expre

SUBMITTER: Dr. Xiaoguang Li 

PROVIDER: S-SCDT-EMBOR-2018-47202V1 | biostudies-other |

REPOSITORIES: biostudies-other