Broad activation of the Parkin pathway induces synaptic mitochondrial deficits in early tauopathy.

ABSTRACT: Mitochondrial defects are a hallmark of early pathophysiology in Alzheimer's disease, with pathologically phosphorylated tau reported to induce mitochondrial toxicity. Mitophagy constitutes a key pathway in mitochondrial quality control by which damaged mitochondria are targeted for autophagy. However, few details are known regarding the intersection of mitophagy and pathologies in tauopathy. Here, by applying biochemical and cell biological approaches including time-lapse confocal imaging in live tauopathy neurons, combined with gene rescue experiments via stereotactic injections of adeno-associated virus particles into tauopathy mouse brains, electrophysiological recordings and behavioural tests, we demonstrate for the first time that mitochondrial distribution deficits at presynaptic te

SUBMITTER: Jeong YY 

PROVIDER: S-EPMC8967101 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature