Unfolding the Mystery of Parkinson’s Disease

Alpha-synuclein is a little-understood protein found in neural tissue in many parts of the brain. It’s also a key protein associated with Parkinson’s disease, an incurable degenerative brain disorder that afflicts a half-million Americans. For the first time ever, researchers in the Petsko-Ringe and Pochapsky laboratories at Brandeis have produced and determined the normal structure of alpha-synuclein — a critical first step to understanding its role in Parkinson’s.

While people with Parkinson’s show outward symptoms, the definitive diagnosis is made post-mortem, when the brain reveals the hallmark of the disease: abnormal clumps of tangled strands of alpha-synuclein, known as Lewy bodies, instead of the tidy, folded molecules of normal proteins. Abnormal alpha-synuclein is also thought to be involved in Lewy body dementia, a relative of Parkinson’s that affects another 1 million Americans.

“We don’t really know whether the clumps are a side effect or whether they’re the cause of Parkinson’s disease, but we do know that the masses of alpha-synuclein proteins are always there in the patients’ brains,” says Thomas C. Pochapsky, professor of chemistry and an author of a paper reporting the labs’ research in the Proceedings of the National Academy of Sciences.

The labs’ discovery opens the door to the potential development of promising therapies. One possible treatment might be a drug that “glues” together the molecules of the protein to prevent them from clumping up. A strategy to improve diagnosis, says Dagmar Ringe, professor of biochemistry and chemistry, might involve monitoring levels of alpha-synuclein in patients suspected of having Parkinson’s or Lewy body dementia.

— Susan Chaityn Lebovits

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