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PMID:20483372

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Citation

Saini, N, Oelhafen, S, Hua, H, Georgiev, O, Schaffner, W and Büeler, H (2010) Extended lifespan of Drosophila parkin mutants through sequestration of redox-active metals and enhancement of anti-oxidative pathways. Neurobiol. Dis. 40:82-92

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.

Links

PubMed Online version:10.1016/j.nbd.2010.05.011

Keywords

Animals; Central Nervous System/drug effects; Central Nervous System/metabolism; Disease Models, Animal; Drosophila Proteins/deficiency; Drosophila Proteins/genetics; Drosophila melanogaster/genetics; Longevity/drug effects; Longevity/genetics; Mutation/genetics; Neurons/drug effects; Neurons/metabolism; Parkinson Disease/genetics; Parkinson Disease/metabolism; Ubiquitin-Protein Ligases/deficiency; Ubiquitin-Protein Ligases/genetics

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DROME:PRKN

involved_in

GO:1900407: regulation of cellular response to oxidative stress

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q7KTX7

involved_in

GO:1900407: regulation of cellular response to oxidative stress

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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