Study Rationale:
Alpha-synuclein is a sticky protein that clumps in the brains of people with Parkinson's disease (PD). Researchers believe that alpha-synuclein clumps can damage nerve cells in the brain. Thus, the removal of alpha-synuclein from the brain has been studied extensively as a treatment for PD. Alpha-synuclein clumping has another damaging consequence: It draws alpha-synuclein away from synaptic vesicles, small sacks within a nerve cell to which alpha-synuclein is normally attached. Being attached to synaptic vesicles enables alpha-synuclein's vital function: to maintain communication between nerve cells. The loss of this function because of clumping may in part cause PD.
Hypothesis:
We aim to determine how attachment of alpha-synuclein to synaptic vesicles affects the health and survival of nerve cell. We hypothesize that supporting the attachment of alpha-synuclein to synaptic vesicles reduces its clumping and associated harmful effects.
Study Design:
We will test our hypothesis by first developing stickier forms of alpha-synuclein, which attach themselves to synaptic vesicles more readily. We will then characterize the function and clumping of these forms in vitro. Lastly, we will analyze the effect of these alpha-synuclein forms on the health and survival of nerve cell in pre-clinical models.
Impact on Diagnosis/Treatment of Parkinson's Disease:
If successful, our study will determine how the attachment of alpha-synuclein to synaptic vesicles affects the health and survival of nerve cells. It may also suggest new Parkinson's treatment strategies.
Next Steps for Development:
Our study will establish the foundation for a targeted treatment strategy that is not based on removing alpha-synuclein from the brain but on keeping alpha-synuclein attached to synaptic vesicles.