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




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BMC Neuroscience

, 18:46

Neurobiology of 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 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.

KeywordsSIRT1 Oxidative stress Cell survival Alpha-synuclein Parkinson’s disease AbbreviationsSIRT1sirtuin 1

SIR2silent information regulator 2

NADnicotinamide adenine dinucleotide

ROSreactive oxygen species

PDParkinson’s disease

PDDParkinson’s disease with dementia

DLBdementia with Lewy bodies

ADAlzheimer’s disease

NF-κBnuclear factor kappa-light-chain-enhancer of activated B cells

FOXOforkhead box

PGC-1aperoxisome proliferator-activated receptor gamma coactivator 1-alpha

PBSphosphate buffered saline

DMSOdimethyl sulfoxide

TBStris buffered saline

PEIpolyethyleneimine

NAMnicotinamide

FCXfrontal cortex

TCXtemporal cortex

Cbcerebellum

Puputamen

Hphippocampus

PMDpost-mortem delay

Electronic supplementary materialThe online version of this article doi:10.1186-s12868-017-0364-1 contains supplementary material, which is available to authorized users.





Autor: Preeti Singh - Peter S. Hanson - Christopher M. Morris

Fuente: https://link.springer.com/







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