Stimulation of synaptic activity promotes TFEB-mediated clearance of pathological MAPT/Tau in cellular and mouse models of tauopathies.

ABSTRACT: Synapses represent an important target of Alzheimer disease (AD), and alterations of their excitability are among the earliest changes associated with AD development. Synaptic activation has been shown to be protective in models of AD, and deep brain stimulation (DBS), a surgical strategy that modulates neuronal activity to treat neurological and psychiatric disorders, produced positive effects in AD patients. However, the molecular mechanisms underlying the protective role(s) of brain stimulation are still elusive. We have previously demonstrated that induction of synaptic activity exerts protection in mouse models of AD and frontotemporal dementia (FTD) by enhancing the macroautophagy/autophagy flux and lysosomal degradation of pathological MAPT/Tau. We now provide evidence that TFEB (tr

SUBMITTER: Akwa Y 

PROVIDER: S-EPMC9851246 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature