"Parkinson's" in a Transgenic <I>Drosophila</I>
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Mel Feany and Welcome Bender of Harvard Medical School have succeeded in creating a transgenic Drosophila melanogaster model of Parkinson's, and surprisingly, have demonstrated that the flies feature all the hallmarks of the human disease. The researchers inserted a copy of the gene for human α-synuclein, a protein that has been linked to a familial form of Parkinson's disease. The flies reached adulthood seemingly normal. But between the ages of 30 and 60 days, the second half of Drosophila's lifespan, the flies lost their dopaminergic neurons, showed α-synuclein containing inclusions (similar to Lewy bodies) in their neurons, and exhibited locomotor dysfunction, all features of human Parkinson's. The damage seems to be selective, as the nervous system in these flies appears to develop normally and there is no widespread cell death in the brains of aged transgenic flies.
"We will now be able to delineate underlying pathogenetic mechanisms and identify novel proteins mediating α-synuclein toxicity in a genetically tractable organism," write the authors. In an accompanying News and Views article, Christian Haass and Philipp Kahle of Ludwig Maximilians University in Munich add that "The short generation time of flies make them invaluable tools for drug screening."—Hakon Heimer
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Papers
- Pereira AC, Huddleston DE, Brickman AM, Sosunov AA, Hen R, McKhann GM, Sloan R, Gage FH, Brown TR, Small SA. An in vivo correlate of exercise-induced neurogenesis in the adult dentate gyrus. Proc Natl Acad Sci U S A. 2007 Mar 27;104(13):5638-43. PubMed.
- Pereira AC, Wu W, Small SA. Imaging-guided microarray: isolating molecular profiles that dissociate Alzheimer's disease from normal aging. Ann N Y Acad Sci. 2007 Feb;1097:225-38. PubMed.
- Small SA, Tsai WY, DeLaPaz R, Mayeux R, Stern Y. Imaging hippocampal function across the human life span: is memory decline normal or not?. Ann Neurol. 2002 Mar;51(3):290-5. PubMed.
Primary Papers
- Feany MB, Bender WW. A Drosophila model of Parkinson's disease. Nature. 2000 Mar 23;404(6776):394-8. PubMed.
- Haass C, Kahle PJ. Parkinson's pathology in a fly. Nature. 2000 Mar 23;404(6776):341, 343. PubMed.
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