SIRT1 ameliorates oxidative stress induced neural cell death and is down-regulated in Parkinson’s disease
Abstract Background Sirtuins (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 S...
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doaj-a682de07cb2949c2bddf0c9f2b5670c92020-11-24T21:43:26ZengBMCBMC Neuroscience1471-22022017-06-0118111310.1186/s12868-017-0364-1SIRT1 ameliorates oxidative stress induced neural cell death and is down-regulated in Parkinson’s diseasePreeti Singh0Peter S. Hanson1Christopher M. Morris2Medical Toxicology Centre, and NIHR Health Protection Research Unit in Chemical and Radiation Threats and Hazards, Newcastle UniversityMedical Toxicology Centre, and NIHR Health Protection Research Unit in Chemical and Radiation Threats and Hazards, Newcastle UniversityMedical Toxicology Centre, and NIHR Health Protection Research Unit in Chemical and Radiation Threats and Hazards, Newcastle UniversityAbstract Background Sirtuins (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. Results Over-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. Conclusions These 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.http://link.springer.com/article/10.1186/s12868-017-0364-1SIRT1Oxidative stressCell survivalAlpha-synucleinParkinson’s disease |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Preeti Singh Peter S. Hanson Christopher M. Morris |
spellingShingle |
Preeti Singh Peter S. Hanson Christopher M. Morris SIRT1 ameliorates oxidative stress induced neural cell death and is down-regulated in Parkinson’s disease BMC Neuroscience SIRT1 Oxidative stress Cell survival Alpha-synuclein Parkinson’s disease |
author_facet |
Preeti Singh Peter S. Hanson Christopher M. Morris |
author_sort |
Preeti Singh |
title |
SIRT1 ameliorates oxidative stress induced neural cell death and is down-regulated in Parkinson’s disease |
title_short |
SIRT1 ameliorates oxidative stress induced neural cell death and is down-regulated in Parkinson’s disease |
title_full |
SIRT1 ameliorates oxidative stress induced neural cell death and is down-regulated in Parkinson’s disease |
title_fullStr |
SIRT1 ameliorates oxidative stress induced neural cell death and is down-regulated in Parkinson’s disease |
title_full_unstemmed |
SIRT1 ameliorates oxidative stress induced neural cell death and is down-regulated in Parkinson’s disease |
title_sort |
sirt1 ameliorates oxidative stress induced neural cell death and is down-regulated in parkinson’s disease |
publisher |
BMC |
series |
BMC Neuroscience |
issn |
1471-2202 |
publishDate |
2017-06-01 |
description |
Abstract Background Sirtuins (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. Results Over-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. Conclusions These 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. |
topic |
SIRT1 Oxidative stress Cell survival Alpha-synuclein Parkinson’s disease |
url |
http://link.springer.com/article/10.1186/s12868-017-0364-1 |
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