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SIRT1 ameliorates oxidative stress induced neural cell death and is down-regulated in Parkinson’s disease

Lookup NU author(s): Dr Preeti Singh, Dr Peter Hanson, Dr Christopher Morris

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

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.


Publication metadata

Author(s): Singh P, Hanson PS, Morris CM

Publication type: Article

Publication status: Published

Journal: BMC Neuroscience

Year: 2017

Volume: 18

Issue: 1

Online publication date: 02/06/2017

Acceptance date: 27/05/2017

ISSN (electronic): 1471-2202

Publisher: BioMed Central Ltd

URL: https://doi.org/10.1186/s12868-017-0364-1

DOI: 10.1186/s12868-017-0364-1

PubMed id: 28578695


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