Steps toward a Parkinson's cure

While little is known about the function of the protein alpha-synuclein in healthy brains, it is present not only in the abnormal protein clusters that characterize Parkinson’s disease called Lewy bodies, but also in protein deposits associated with Alzheimer’s disease.

The same molecular process applied to different proteins is suspected to be at the root of other incurable neurological diseases including Huntington’s, ALS and Creutzfeldt-Jakob disease.

Computer rendering of alpha-synuclein proteins.
Alpha-synuclein proteins aggregating into clusters

Chemistry and Biochemistry Professor David Talaga has received a $283,000, one-year “bridging award” from the National Institute of Neurological Disorders and Stroke to study the interfacially activated aggregation of alpha-synuclein. This additional data will help him build the case for his five-year research project grant application to study the aggregation of proteins on surfaces that can lead to the formation of plaque in cells implicated in neurological diseases.

“Aggregation is when proteins form a tightly bound group that can grow into a slender fiber, or fibril. By focusing on how solid-liquid interfaces influence the aggregation and fibrillization of alpha-synuclein, Talaga hopes to identify the molecular steps that initiate the process.

“If we can find the component of the cell that initiates the pathological structural change in alpha-synuclein, then we can look for a drug that would either prevent binding or lower the concentration of that component,” Talaga says. “And if we understand the way that aggregates spread from cell to cell, we can look for drugs that inhibit the cellular mechanism responsible for cell-to-cell transmission of aggregates.”

Talaga’s research provides crucial understanding into the first molecular steps in the development of Parkinson’s disease. “Our hope is that understanding these steps will allow us to design therapies that prevent or reverse them,” he says. “Without this basic scientific level of understanding, trying to find a therapy is like shooting in the dark.”