Lake Forest College, Lake Forest, IL 60045
Parkinson’s disease (PD) is a neurodegenerative disorder marked by the progressive loss of voluntary muscle control, followed by cognitive decline. PD results from the death of dopamine-producing midbrain cells linked to the misfolding and aggregation of the protein α-synuclein. While 140 amino acids comprise α-synuclein, only a subset of them are likely of high pathological importance. Another member of our lab, Katrina Campbell, initially studied the prospective contribution of five such amino acids (D2, A76, V77, Q79, E83) in budding yeast, by individually mutating each one, and found that each amino acid was indeed influential in determining α-synuclein's ability to associate with membranes and to aggregate (both are PD linked characteristics). I am furthering this work by studying these same five mutants in fission yeast, a second PD model developed in our lab. I have also added two more amino acids (K96, K102) to our analysis that may be critical in controlling α-synuclein toxicity through the post-translational modification SUMOylation.
[Abstract (DOC)]