Study Rationale:
Many of the proteins implicated in Parkinson’s disease appear to have a role at the nerve terminal, presumably in neurotransmitter release. However, the function of most has remained unclear, making it difficult to understand their role in normal physiology as well as in degeneration.
Hypothesis:
We hypothesize that the major proteins implicated in Parkinson’s disease (e.g., alpha-synuclein) influence a cellular process called exo- and endocytosis of synaptic vesicles. We will also test the hypothesis that this occurs through changes in their composition.
Study Design:
The program uses a combination of live imaging, electron microscopy and proteomics to characterize the role of Parkinson’s disease proteins in neurotransmitter release.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
Understanding how Parkinson’s disease proteins influence function of the nerve terminal may enable us to identify factors that modify this process and reverse or prevent degeneration.
Next Steps for Development:
The next steps are to identify cellular factors that cooperate with alpha-synuclein in health and in disease. These represent potential targets for therapeutic intervention. By comparing the effect of other Parkinson’s-associated proteins on synaptic vesicle cycling, we will identify common places for additional intervention.