Study Rationale:
Alpha-synuclein, the sticky protein that clumps in the cells of people with Parkinson's disease (PD), has long been implicated in the development of PD. Alpha-synuclein clumps vary in size, but only oligomers -- small clumps -- are believed to be the most damaging form of this protein that kills nerve cells in Parkinson's disease. However, hardly any information about oligomers exists, and their origin and location within the cell remains unknown.
Hypothesis:
Using oligomers created in a test tube and the MJF14 antibody -- another protein that binds to oligomers and serves as a label in showing their location -- we will study oligomer structure and development. We will also evaluate whether MJF14 is able to prevent damage and death of brain cells.
Study Design:
Sophisticated technology, including an extremely precise microscope, will be used to study the structure of alpha-synuclein oligomers. Also, we will develop special techniques to show oligomers in brain cells and tissue. Using an in vitro model of PD, we will evaluate the ability of MJF14 to prevent damage and death of brain cells.
Impact on Diagnosis/Treatment of Parkinson's disease:
Knowing the structure of toxic alpha-synuclein oligomers will be instrumental in developing better tools to measure their quantity in patient samples with the goal of tracking the disease progression and response to treatment.
Next Steps for Development:
Knowing the structure of toxic alpha-synuclein oligomers will be instrumental in developing new PD biomarkers -- measures of disease -- as well as treatments.