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Explore the genetic connections of Pink1/Parkin pathway in Parkinson’s Disease through a Drosophila study focusing on mitochondrial function, muscle degeneration, and neuronal health. Discover the implications and potential treatment avenues.
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Parkinson’s Disease: A genetic screen to investigate the Pink1/Parkin pathway in Drosophila Justin Hayase MSTAR Presentation Guo Lab July 23,2009
Parkinson’s Disease • Degeneration of the substantia nigra • Resting tremor, bradykinesia, rigidity, postural instability • 1-2% of the population • 95% sporadic, 5% familial • Major treatment is dopamine replacement
Familial Parkinson’s • Pink1 – PTEN induced kinase 1 • Parkin – E3 ligase • α-synuclein • LRRK-2 • DJ-1 • ATP13A2 Parkin Pink1
Pink1 Mutant Flies • Male sterility • Mitochondrial defects • Muscle degeneration • Dopaminergic neuronal degeneration • Increased sensitivity to ROS • Functional conservation between humans and flies Ira E. Clark, et al. Nature 441, 1162-1166(29 June 2006)
Materials and Methods • Unbiased genetic screen • ~200 RNAi lines from the Laski lab • Crossed to 705f (Pink1 mutant) • Characterization of the indirect flight muscle • Mitochondrial morphology
Conclusions • This is just the beginning! • Identification of ~6 genes for further investigation • Mitochondrial role in neurodegenerative processes – not just the substantia nigra!
Acknowledgements • Dr. Ming Guo • Lok Leung • The Guo Lab Thank you!