Study Rationale:
The protein alpha-synuclein has a central, causative role in Parkinson's disease, but we do not understand how it contributes to cell degeneration. Mutations in the gene (SNCA) that encodes alpha-synuclein cause a rare hereditary form of the disease and provide an invaluable way to understand its role. We will study how these mutations affect the function of alpha-synuclein.
Hypothesis:
We hypothesize that the mutations causing Parkinson's disease all affect a common property of alpha-synuclein, thereby causing disease.
Study Design:
It has not previously been possible to test the effect of mutations on alpha-synuclein function because the function was not known. We will use a new laboratory test we have recently developed to determine how the mutations affect function, and if they do, determine the mechanism.
Impact on Diagnosis/Treatment of Parkinson's Disease:
The primary, causative role of alpha-synuclein in Parkinson's disease suggests that manipulating the function of the protein has great therapeutic potential.
Next Steps for Development:
We can screen for other proteins or manipulations that reverse the effect of alpha-synuclein changes.