Arun George Paul '05
Ruja Shrestha '07
Parkinson's Disease, α-synuclein misfolding
Parkinson disease (PD) is caused by α-synuclein misfolding in the substantia nigra par compacta cells of the brain. A recent study (Willingham et. al., 2003) demonstrated that over-expression of wild type (WT) α-synuclein in STP2 deletion (STP2Δ) S. cerevisiae strains is toxic. Surprisingly, we did not observe any toxicity in 4741 (parent strain) and STP2Δ strains over-expressing WT α-synuclein or its mutant forms. Moreover, GFP microscopy of α-synuclein in STP2Δ strains showed phenotypes observed in strains with STP2. We observed halos for strains over-expressing WT α-synuclein and the A53T mutant. α-Synuclein was cytoplasmic for strains with the A30P mutant and the A30P/A53T double mutant. Western analysis demonstrated that neither the levels of α-synuclein expression nor the levels of GAPDH, a pro-apoptotic protein changed in STP2Δ strains. Furthermore, genetic deletion of GAPDH did not show any enhanced growth in strains that overexpressed α-synuclein. The lack of α-synuclein toxicity in STP2Δin our study may be due to our use of a different overexpression system, which did not yield amounts high enough to overwhelm protein quality-control systems and yield the toxicity that underlies PD pathogenesis (Berke, 2003) of the cell.
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