Insight Into Parkinson\u27s Disease: Does alpha-Synuclein Use the MVB/Endocytosis Pathway as a Route for Degradation in the Lysosome?

Parkinson’s disease is a fatal and incurable human neurodegenerative disorder that destroys midbrain neurons. The misfolding, accumulation, and aggregation of the protein alpha-synuclein is thought to kill these cells. Enhancing alpha-synuclein degradation may help prevent its accumulation and aggregation, while protecting cells against toxicity. For this thesis, we used the model organism budding yeast to evaluate the hypothesis that alpha-synuclein is degraded by the cellular organelle lysosome via a specific route: the MVB/endocytosis pathway. Specifically, we evaluated whether three disease-related properties of alpha-synuclein (aggregation, accumulation, and toxicity) worsened in yeast strains that were individually deleted for genes coding for proteins required for the MVB/endocytosis pathway. In support of our hypothesis, each gene deletion altered one or more alpha-synuclein properties. While our data indicates that the MVB pathway is a route for alpha-synuclein degradation, the specificity and extent of alpha-synuclein involvement with proteins within the ESCRT complexes appears unexpectedly complex