Earlier this summer, a team of researchers led by Dennis J. Selkoe of Harvard Medical School published a potentially significant finding in Nature suggesting that alpha-synuclein, the protein that aggregates into insoluble fibrils within Lewy bodies in patients with Parkinson’s disease, has been mischaracterized. In contrast previous understanding of alpha-synuclein as a natively unstructured protein, Selkoe and his lab proposed that alpha-synuclein naturally exists as a stable tetramer before destabilization and pathological aggregation. In a push forward in Parkinson’s disease research, a recent independent study by the Petsko-Ringe and Pochapsky laboratories at Brandeis University in Waltham, MA, confirmed the hypothesis by Selkoe and colleagues. The finding is supported by analytical techniques--namely NMR and circular dichroism spectroscopy--different from the Selkoe lab and is published in the October 25 issue of the Proceedings of the National Academy of Sciences.

While people with Parkinson’s diseases exhibit many obvious symptoms such as tremors and weakness of face and throat muscles, definitive diagnosis of Parkinson’s comes post mortem, when alpha-synuclein proteins become denatured and form clumps called Lewy bodies in the brain.

“We don’t really know whether this is a side effect or whether it’s the cause of Parkinson’s disease, but we do know that the clumps of proteins are always there,” says Thomas C. Pochapsky, professor of chemistry and one of the authors of the paper. Pochapsky’s lab was responsible for examining the protein using nuclear magnetic resonance, a sort of MRI for molecules, housed at the Landsman Research Facility.

Alpha-synuclein is found in large quantities in the brain. Its association with Parkinson’s disease has stirred curiosity since it was discovered in 1997. 


“Nobody knows what it does, but there’s a lot of it,” says Pochapsky. “The question is whether the unfolded or coagulated Lewy body protein just represents the pathological form of something that’s normally doing something.”

Read more from the official press release by Brandeis University.
Full original open access research article available here