Study Rationale:
The alpha-synuclein protein forms oligomers (protein clumps) that cause toxicity in the brains of individuals with Parkinson’s disease (PD). We have developed methods that can measure these toxic changes in brain cells grown in a petri dish. We aim to identify a drug candidate capable of preventing these toxic effects.
Hypothesis:
We hypothesize that drug candidates can effectively prevent many of the toxic changes caused by alpha-synuclein oligomers.
Study Design:
We have developed techniques that can measure changes in the alpha-synuclein protein. By applying the toxic alpha-synuclein oligomers to brain cells grown for several weeks in a petri dish, we can evaluate the oligomers' effects on the normal movement of the plasma membrane (border between the cell and its environment) compartments in the cell. When the normal movement of the plasma membrane is altered, brain cells have difficulty communicating with each other, which can lead to dementia. By using this cellular model, we can test the effect of different compounds and identify candidate drugs that might prevent the toxic effects of this protein.
Impact on Diagnosis/Treatment of Parkinson's Disease:
There are no drugs available that can prevent the effects of alpha-synuclein oligomers on brain cells. Compounds that are capable of stopping this toxicity have the potential to slow the progression of Parkinson’s.
Next Steps for Development:
Success in this project will enable us to develop an initial candidate into a new potential therapy by iteratively changing individual molecules and retesting them in our “Parkinson’s in a dish” model. The effects of the drug on cognitive dysfunction, which characterizes Parkinson’s dementia, will then be evaluated.