Mitochondrial SIRT3 Deficiency Results in Neuronal Network Hyperexcitability, Accelerates Age-Related Aβ Pathology, and Renders Neurons Vulnerable to Aβ Toxicity.

ABSTRACT: Aging is the major risk factor for Alzheimer's disease (AD). Mitochondrial dysfunction and neuronal network hyperexcitability are two age-related alterations implicated in AD pathogenesis. We found that levels of the mitochondrial protein deacetylase sirtuin-3 (SIRT3) are significantly reduced, and consequently mitochondria protein acetylation is increased in brain cells during aging. SIRT3-deficient mice exhibit robust mitochondrial protein hyperacetylation and reduced mitochondrial mass during aging. Moreover, SIRT3-deficient mice exhibit epileptiform and burst-firing electroencephalogram activity indicating neuronal network hyperexcitability. Both aging and SIRT3 deficiency result in increased sensitivity to kainic acid-induced seizures. Exposure of cultured cerebral cortical neurons to

SUBMITTER: Perone I 

PROVIDER: S-EPMC9810471 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature