Yeast helps researchers better understand Parkinson's mystery

CAMBRIDGE, Mass. (Dec. 4, 2003) Scientists know that in patients with Parkinson's disease, certain proteins in the brain form clusters that somehow contribute to cell death and, eventually, lead to the onset of the disease's debilitating symptoms. The quest to figure out how these clusters form and how to prevent them has been slow and difficult.

Now, after years of painstaking research, scientists have succeeded in duplicating the disease's most critical features in the most readily manipulated model organism in existence. In research published in this week's issue of the journal Science, a team from Whitehead Institute for Biomedical Research used common baker's yeast as a living test tube to show how just a small amount of a Parkinson's-related neuronal protein called alpha-synuclein (aSyn) can convince neighboring proteins to abandon their normal shape and form these deadly clusters.

"For the first time we can initiate the process synchronously in living cells and watch what is happening in real time," says Susan Lindquist, director of Whitehead Institute and a lead author of this new study.

A protein's shape is critical to its function: When a protein changes its shape, it changes function, and this can be deadly. Many neurodegenerative diseases such as Parkinson's are thought to be caused by proteins like aSyn that can misfold into abnormal shapes and lose their ability to function correctly or even wreak havoc in the cell.

The Lindquist lab has been studying human proteins in yeast for several years, learning more and more about how proteins misfold and what happens when they do. The similarities in basic cellular processes between humans and yeast were so striking, they decided to see if they could provoke a Parkinson's-like problem in these simple, one-celled fungi.

For the study, Tiago Outeiro (o-TEE-ero), a graduate student in Lindquist's lab and lead author on the paper, assembled a group of yeast cells, e

Contact: Kelli Whitlock or David Cameron
Whitehead Institute for Biomedical Research

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