Extended lifespan of Drosophila parkin mutants through sequestration of redox-active metals and enhancement of anti-oxidative pathways

Abstract The mechanisms underlying neuron death in Parkinson's disease are unknown, but both genetic defects and environmental factors are implicated in its pathogenesis. Mutations in the parkin gene lead to autosomal recessive juvenile Parkinsonism (AR-JP). Here we report that compared to cont...

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Published in:	Neurobiology of disease Vol. 40; no. 1; pp. 82 - 92
Main Authors:	Saini, Nidhi, Oelhafen, Sandra, Hua, Haiqing, Georgiev, Oleg, Schaffner, Walter, Büeler, Hansruedi
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-10-2010 Elsevier
Subjects:	Animals Central Nervous System - drug effects Central Nervous System - metabolism Disease Models, Animal Drosophila Drosophila melanogaster - genetics Drosophila Proteins - deficiency Drosophila Proteins - genetics Longevity - drug effects Longevity - genetics Metal chelators Mutation - genetics Neurology Neurons - drug effects Neurons - metabolism Oxidative stress Parkin Parkinson Disease - genetics Parkinson Disease - metabolism Parkinson's disease Ubiquitin-Protein Ligases - deficiency Ubiquitin-Protein Ligases - genetics Oxidative stress Parkinson's disease Drosophila Metal chelators Parkin
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Summary:	Abstract The mechanisms underlying neuron death in Parkinson's disease are unknown, but both genetic defects and environmental factors are implicated in its pathogenesis. Mutations in the parkin gene lead to autosomal recessive juvenile Parkinsonism (AR-JP). Here we report that compared to control flies, Drosophila lacking parkin show significantly reduced lifespan but no difference in dopamine neuron numbers when raised on food supplemented with environmental pesticides or mitochondrial toxins. Moreover, chelation of redox-active metals, anti-oxidants and overexpression of superoxide dismutase 1 all significantly reversed the reduced longevity of parkin -deficient flies. Finally, parkin deficiency exacerbated the rough eye phenotype of Drosophila caused by overexpression of the copper importer B (Ctr1B) . Taken together, our results demonstrate an important function of parkin in the protection against redox-active metals and pesticides implicated in the etiology of Parkinson's disease. They also corroborate that oxidative stress, perhaps as a consequence of mitochondrial dysfunction, is a major determinant of morbidity in parkin mutant flies.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	0969-9961 1095-953X
DOI:	10.1016/j.nbd.2010.05.011