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

Heather J. M. Weir, Tracey K. Murray, Patrick G. Kehoe, Seth Love, Eric M. Verdin, Michael J. O'Neill, Jon D. Lane*, Nina Balthasar

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

102 Citations (Scopus)

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.
Original languageEnglish
Article numberARTN e48225
Pages (from-to)e48225
Number of pages7
JournalPLoS ONE
Volume7
Issue number11
DOIs
Publication statusPublished - 6 Nov 2012

Structured keywords

  • Dementia Research Group

Keywords

  • MITOCHONDRIAL DYSFUNCTION
  • STRESS
  • AMYLOID PRECURSOR PROTEIN
  • SIRT3-MEDIATED DEACETYLATION
  • OXIDATIVE DAMAGE
  • LYSINE ACETYLATION
  • A-BETA
  • TRANSGENIC MOUSE
  • MECHANISMS
  • RESTRICTION

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  • RCUK FELLOW

    Ulcigrai, C.

    1/08/071/08/12

    Project: Research

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