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Title: Drosophila overexpressing parkin R275W mutant exhibits dopaminergic neuron degeneration and mitochondrial abnormalities
Authors: Wang, C.
Lu, R.
Ouyang, X.
Ho, M.W.L.
Chia, W. 
Yu, F. 
Lim, K.-L.
Keywords: Neuronal death
Parkinson's disease
Issue Date: 8-Aug-2007
Citation: Wang, C., Lu, R., Ouyang, X., Ho, M.W.L., Chia, W., Yu, F., Lim, K.-L. (2007-08-08). Drosophila overexpressing parkin R275W mutant exhibits dopaminergic neuron degeneration and mitochondrial abnormalities. Journal of Neuroscience 27 (32) : 8563-8570. ScholarBank@NUS Repository.
Abstract: Mutations in the parkin gene are a predominant cause of familial parkinsonism. Although initially described as a recessive disorder, emerging evidence suggest that single parkin mutations alone may confer increased susceptibility to Parkinson's disease. To better understand the effects of parkin mutations in vivo, we generated transgenic Drosophila overexpressing two human parkin missense mutants, R275W and G328E. Transgenic flies that overexpress R275W, but not wild-type or G328E, human parkin display an age-dependent degeneration of specific dopaminergic neuronal clusters and concomitant locomotor deficits that accelerate with age or in response to rotenone treatment. Furthermore, R275W mutant flies also exhibit prominent mitochondrial abnormalities in their flight muscles. Interestingly, these defects caused by the expression of human R275W parkin are highly similar to those triggered by the loss of endogenous parkin in parkin null flies. Together, our results provide the first in vivo evidence demonstrating that parkin R275W mutant expression mediates pathogenic outcomes and suggest the interesting possibility that select parkin mutations may directly exert neurotoxicity in vivo. Copyright © 2007 Society for Neuroscience.
Source Title: Journal of Neuroscience
ISSN: 02706474
DOI: 10.1523/JNEUROSCI.0218-07.2007
Appears in Collections:Staff Publications

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