Researchers Gain Better Insight Into Alpha-Synuclein’s Role in Parkinson’s Disease

Researchers have learned more about the true role of alpha-synuclein, a faulty protein involved in the development of Parkinson’s disease. The findings of a recent study add insight into what goes awry in the brain that leads to the onset of this disease.

The study titled, “α-Synuclein promotes dilation of the exocytotic fusion pore,” was published in the journal Nature Neuroscience.

Researchers have known for years that the alpha-synuclein protein has a central role in the development of Parkinson’s disease, as its accumulation becomes toxic to neurons. However, the real function of this protein — its role before the disease kicks in — previously had been unknown.

“The aggregation of alpha-synuclein in neurons is a hallmark of Parkinson’s,” Robert Edwards, MD, the study’s author, said in a news release written by Wallace Ravven. “But we wanted to search for earlier events that might trigger the degenerative process.”

Previous studies had shown that alpha-synuclein is present at the synapses, the connections established between neighboring neurons where the exchange of electrical signals and neuronal communication takes place.

Using mouse neurons and other cells, researchers investigated how alpha-synuclein behaves at the synapses. They found that increasing the expression of this protein inhibits the mechanism through which neurons release vesicles containing molecules to be delivered to other neurons to activate them (neurotransmitters).

In normal levels, however, alpha-synuclein accelerates the release of these molecules if it is already occurring.

Several mutations in the gene encoding alpha-synuclein lead to Parkinson’s disease. According to Edwards, these mutations impair the protein’s normal function by altering its participation in neurotransmitter release.

“So when the negative effect is intact, but the positive role is blocked, the net result disrupts neurotransmitter release,” Edwards said. “This could lead to the impairment in dopamine release, and ultimately to cell death.”

Dopamine is the neurotransmitter lacking in the brains of patients with Parkinson’s disease.

Edwards believes that these defects in alpha-synuclein’s mechanism of action are the reason underlying several cases of Parkinson’s disease that do not involve inherited genetic mutations. Further research is warranted to understand exactly how alpha-synuclein becomes faulty under these conditions.

“By understanding the normal function of alpha-synuclein, and in particular its regulation, we’re starting to understand how anyone can acquire Parkinson’s disease,” Edwards said. “We hope this can help develop therapy that targets the underlying degenerative process.”