Parkinson's Disease, α-synuclein mutation


Parkinson’s disease is a neurodegenerative disorder that is caused by the loss of dopaminergic neurons in the substantia nigra. Misfolding of a-synuclein is thought to cause this selective cell death. In our a-synuclein yeast overexpression model, we previously demonstrated that a-synuclein, is non-toxic to yeast, runs 8-10 kDa higher on protein gels and aggregates minimally in vivo. Recently, a new familial mutant of a-synuclein E46K was discovered. a-Synuclein is a diversely post-translationally modified protein and we hypothesized that one of these modifications may underlie its aberrant size. Here, we show that E46K is more toxic to yeast than other familial a-synuclein mutants. a-Synuclein mutants lacking key phosphorylation and nitrosylation sites are surprisingly toxic as well, but do not account for a-synuclein’s aberrant size. Interestingly, all these mutants localize to the periphery of yeast cells and show variable levels of in vivo aggregation.

SaraHerrera.pps (4885 kB)
PowerPoint Seminar


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