CNS SIRT3 expression is altered by reactive oxygen species and in Alzheimer's disease

PLoS One. 2012;7(11):e48225. doi: 10.1371/journal.pone.0048225. Epub 2012 Nov 6.

Abstract

Progressive mitochondrial dysfunction contributes to neuronal degeneration in age-mediated disease. An essential regulator of mitochondrial function is the deacetylase, sirtuin 3 (SIRT3). Here we investigate a role for CNS Sirt3 in mitochondrial responses to reactive oxygen species (ROS)- and Alzheimer's disease (AD)-mediated stress. Pharmacological augmentation of mitochondrial ROS increases Sirt3 expression in primary hippocampal culture with SIRT3 over-expression being neuroprotective. Furthermore, Sirt3 expression mirrors spatiotemporal deposition of β-amyloid in an AD mouse model and is also upregulated in AD patient temporal neocortex. Thus, our data suggest a role for SIRT3 in mechanisms sensing and tackling ROS- and AD-mediated mitochondrial stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology*
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Central Nervous System / metabolism*
  • Central Nervous System / pathology*
  • Disease Models, Animal
  • Electron Transport
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Lentivirus
  • Mice
  • Mitochondria / metabolism
  • Neuroglia / metabolism
  • Neuroglia / pathology
  • Neurons / metabolism
  • Neurons / pathology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Reactive Oxygen Species / metabolism*
  • Sirtuin 3 / genetics
  • Sirtuin 3 / metabolism
  • Subcellular Fractions / metabolism
  • Up-Regulation / genetics

Substances

  • Amyloid beta-Peptides
  • RNA, Messenger
  • Reactive Oxygen Species
  • Sirtuin 3