A group of researchers from the Petsko-Ringe and Pochapsky laboratories have produced and determined the structure of alpha-synuclein, a key protein associated with Parkinson's disease, according to an Oct. 21 BrandeisNOW press release.

Their findings, which were recently published in the Proceedings of the National Academy of Sciences, provide information that may someday be used to produce a new kind of treatment for the incurable degenerative disease, according to BrandeisNOW.

More than half a million Americans suffer from Parkinson's disease, and about 50,000 new cases are reported annually, according to the National Institute of Health.

While Parkinson's patients present typical symptoms such as tremors and weakness in facial and throat muscles, the press release explains that the characteristic diagnosis of the disease is only discovered post-mortem, when the alpha-synuclein proteins become denatured and form clumps called Lewy bodies in the brain.

Prof. Thomas Pochapsky (CHEM) and one of the authors of the paper, said in the press release, "We don't really know whether [the alpha-synuclein] 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."

In an interview with the Justice, Pochapsky spoke about the impetus behind studying the alpha-synuclein protein.

"No one really knows what it [alpha-synuclein] does, but we do know that it misbehaves in Parkinson's," said Pochapsky. "So the motivation was to try and figure out what this thing actually looks like under normal circumstances, when it's not denatured or misbehaving; because if you can stabilize it, in its good form, whatever that form may be, you can slow it down and maybe even reverse Parkinson's."

"The question is whether the unfolded or coagulated Lewy body protein just represents the pathological form of something that's normally doing something," Pochapsky said in the BrandeisNOW press release.

In the BrandeisNOW press release, Prof. Gregory Petsko (BCHM) compared alpha-synuclein to an origami bird that is harmless when folded but dangerous when unfolded. This knowledge may someday lead to the development of drug therapies that act like glue, helping the protein maintain its shape.

While some drug therapies perform in this manner in the treatment of other diseases, the possibility of one for Parkinson's has not yet been discovered, or even investigated, because until now, scientists and researchers thought the Parkinson's protein lacked structure.

The possibility that the protein does have a structure means that an approach can now be considered, according to the press release.

Quyen Hoang, who was a post-doctoral researcher in the Petsko-Ringe lab and is continuing with the research in his own lab at Indiana University School of Medicine, played a key role in developing the methodology to produce the protein.

In an email to the Justice, Hoang described his involvement.

"A traditional method for isolating alpha-synuclein involves boiling the protein sample," explained Hoang. "I felt that the boiling step could denature the protein; therefore, I developed a purification procedure that avoided the need for boiling, thereby maintaining the protein in its native form."

Hoang added that his research is important at the molecular level.

"Now that we understand a little more about the disease [Parkinson's] process at the molecular level, we can start to think of ways to alter the course of the disease," wrote Hoang.