Saini, N; Oelhafen, S; Hua, H; Georgiev, O; Schaffner, W; Büeler, H (2010). Extended lifespan of Drosophila parkin mutants through sequestration of redox-active metals and enhancement of anti-oxidative pathways. Neurobiology of Disease, 40(1):82-92.
Full text not available from this repository.
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.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||07 Faculty of Science > Institute of Molecular Life Sciences|
|DDC:||570 Life sciences; biology|
|Deposited On:||09 Nov 2010 17:35|
|Last Modified:||27 Nov 2013 21:39|
|Citations:||Web of Science®. Times cited: 18|
Users (please log in): suggest update or correction for this item
Repository Staff Only: item control page