Evaluation of alpha-synuclein splice variants in yeast to better understand Parkinson’s Disease

Parkinson\u27s disease (PD) is a hypokinetic disorder characterized by midbrain neuron loss that results from misfolded α-synuclein. Till recently, full-length α-synuclein was considered the diseased form. Recently, smaller variants of α-synuclein formed through alternative splicing (α-syn 126, α-syn 112, and α-syn 98) have been found in patients, but their significance in unclear. We hypothesized that these splice variants contribute to PD because they lack regions important for function. We will explain how we created these variants this past year to study them in a yeast model. We next plan to evaluate whether they are more toxic than the full-length form