title: CNS SIRT3 expression is altered by reactive oxygen species and in Alzheimer's disease.
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.
authors.affiliation: School of Biochemistry, University of Bristol, Bristol, United Kingdom.
authors.forename: Heather J M
authors.initials: HJ
authors.lastname: Weir
authors.forename: Tracey K
authors.initials: TK
authors.lastname: Murray
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Kehoe
authors.forename: Seth
authors.initials: S
authors.lastname: Love
authors.forename: Eric M
authors.initials: EM
authors.lastname: Verdin
authors.forename: Michael J
authors.initials: MJ
authors.lastname: O'Neill
authors.forename: Jon D
authors.initials: JD
authors.lastname: Lane
authors.forename: Nina
authors.initials: N
authors.lastname: Balthasar
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D002490:Central Nervous System / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D004579:Electron Transport; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D016086:Lentivirus; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D056566:Sirtuin 3 / Q000235:genetics / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
chemical_list: D016229:Amyloid beta-Peptides; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D056566:Sirtuin 3