Parkinson

1
Parkinsons Disease A genetic screen to
investigate the Pink1/Parkin pathway in Drosophila

• Justin Hayase
• MSTAR Presentation
• Guo Lab
• July 23,2009

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Parkinsons 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

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Familial Parkinsons

• Pink1 PTEN induced kinase 1
• Parkin E3 ligase
• a-synuclein
• LRRK-2
• DJ-1
• ATP13A2

Parkin
Pink1
4
How can flies be used to study Parkinsons
Disease?
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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)
6
What are other players in the Pink1/Parkin
pathway?
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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

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Results
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Conclusions

• This is just the beginning!
• Identification of 6 genes for further
  investigation
• Mitochondrial role in neurodegenerative processes
  not just the substantia nigra!

10
Acknowledgements

• Dr. Ming Guo
• Lok Leung
• The Guo Lab

Thank you!