Lookup NU author(s): Dr Preeti Singh,
Dr Peter Hanson,
Dr Christopher Morris
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
BackgroundSirtuins (SIRTs) are NAD+ dependent lysine deacetylases which are conserved from bacteria to humans and have been associated with longevity and lifespan extension. SIRT1, the best studied mammalian SIRT is involved in many physiological and pathological processes and changes in SIRT1 have been implicated in neurodegenerative disorders, with SIRT1 having a suggested protective role in Parkinson’s disease. In this study, we determined the effect of SIRT1 on cell survival and α-synuclein aggregate formation in SH-SY5Y cells following oxidative stress.ResultsOver-expression of SIRT1 protected SH-SY5Y cells from toxin induced cell death and the protection conferred by SIRT1 was partially independent of its deacetylase activity, which was associated with the repression of NF-кB and cPARP expression. SIRT1 reduced the formation of α-synuclein aggregates but showed minimal co-localisation with α-synuclein. In post-mortem brain tissue obtained from patients with Parkinson’s disease, Parkinson’s disease with dementia, dementia with Lewy bodies and Alzheimer’s disease, the activity of SIRT1 was observed to be down-regulated.ConclusionsThese findings suggests a negative effect of oxidative stress in neurodegenerative disorders and possibly explain the reduced activity of SIRT1 in neurodegenerative disorders. Our study shows that SIRT1 is a pro-survival protein that is downregulated under cellular stress.
Author(s): Singh P, Hanson PS, Morris CM
Publication type: Article
Publication status: Published
Journal: BMC Neuroscience
Online publication date: 02/06/2017
Acceptance date: 27/05/2017
Date deposited: 05/07/2017
ISSN (electronic): 1471-2202
Publisher: BioMed Central Ltd
PubMed id: 28578695
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