Rasagiline protects against alpha-synuclein induced sensitivity to oxidative stress in dopaminergic cells.

Neurochemistry International
K Y ChauAnthony H V Schapira

Abstract

Rasagiline is a propargylamine and irreversible monoamine oxidase (MAO) B inhibitor used for the treatment of Parkinson's disease (PD). It has demonstrated neuroprotective properties in laboratory studies. Current concepts of PD aetiopathogenesis include the role of alpha-synuclein, protein aggregation, free radical metabolism and mitochondrial dysfunction in contributing to cell death. We have used a combination of alpha-synuclein and free radical mediated toxicity in a dopaminergic cell line to provide a model of nigral toxicity in order to investigate the potential molecular mechanisms that mediate rasagiline protection. We demonstrate that rasagiline protects against cell death induced by the combination of free radicals generated by paraquat and either wild-type or A53T mutant alpha-synuclein over-expression. This protection was associated with a reduction in caspase 3 activation, a reduction in superoxide generation and a trend to ameliorate the fall in mitochondrial membrane potential. Rasagiline induced an increase in cellular glutathione levels. The results support a role for rasagiline in protecting dopaminergic cells against free radical mediated damage and apoptosis in the presence of alpha-synuclein over-expression...Continue Reading

References

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Dec 23, 2008·Journal of the Neurological Sciences·Kai-Yin ChauAnthony H V Schapira

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Citations

Mar 1, 2012·Antioxidants & Redox Signaling·Aracely Garcia-GarciaRodrigo Franco
Jun 28, 2012·Human Molecular Genetics·Tatiana D PapkovskaiaJ Mark Cooper
Aug 5, 2011·Drugs & Aging·Claire Henchcliffe, W Lawrence Severt
Sep 29, 2011·Movement Disorders : Official Journal of the Movement Disorder Society·Peter Jenner, J William Langston
Nov 10, 2011·The Mount Sinai Journal of Medicine, New York·Anthony H V Schapira
Aug 2, 2011·Free Radical Biology & Medicine·A CzerniczyniecS Lores-Arnaiz
May 6, 2016·Scientific Reports·Chien Tai HongAnthony H V Schapira
Aug 27, 2016·Scientific Reports·Chien Tai HongAnthony H V Schapira
Dec 17, 2014·ACS Chemical Neuroscience·Joe KakishJeremy S Lee
Jun 27, 2017·The World Journal of Biological Psychiatry : the Official Journal of the World Federation of Societies of Biological Psychiatry·Siu W TangBrian E Leonard
Jun 29, 2017·International Clinical Psychopharmacology·Siu W TangBrain E Leonard
Jul 1, 2021·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Chukwunonso K NwabufoEd S Krol

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Methods Mentioned

BETA
protein assays
protein assay

Software Mentioned

ADAGIO

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