From bread to brain: Yeast cells help fight neurodegenerative diseases

By Joshua Sheetz

Yeast may help scientists study diseases that destroy brain cells such as this one. Credit: MIT

CHICAGO — A kitchen cupboard staple is helping in the fight against age-related brain disorders. Yeast has given rise to powerful new methods for examining cellular processes involved in diseases such as Alzheimer’s and Parkinson’s diseases, and for identifying new drug therapies.

No cure exists for these complex diseases, which result when critical nerve cell proteins misfold to form harmful clumps of material, called plaques. But yeast, used for millennia to produce bread and beer, shows great promise as a drug discovery platform, said MIT molecular biologist Susan Lindquist during the Feb. 16 keynote address at the American Association for the Advancement of Science annual meeting in Chicago.

“We [had] the idea that we might be able to use yeast cells as living test tubes,” said Lindquist, a member and past director of MIT’s Whitehead Institute for Biomedical Research.

Yeast genes that are analogous to human genes gave Lindquist and her team a convenient way to screen compounds for their ability to fight neurodegenerative diseases. Since the screening was done in living cells in which complex processes continue to churn, it better mimicked the would-be action of the drugs than traditional test tube studies.

“If you look at some of the biggest blockbuster drugs that we have on the market — they work just as well in a yeast cell as they do in a nerve cell,” Lindquist said.

To program yeast cells to act like the neurons of Alzheimer’s or Parkinson’s patients, the researchers tricked the cells into producing an overabundance of a protein called alpha-synuclein, which is implicated in a number of neurodegenerative disorders. At normal levels, alpha-synuclein plays a poorly understood role in cell signaling. But at high levels, it leads to the formation of toxic plaques. The team tested more than 190,000 compounds to see which could tackle the alpha-synuclein-laced cells. One called N-aryl benzimidazole, or NAB, stood out.

Cells treated with NAB functioned normally and did not form plaques — even at high levels of alpha-synuclein. NAB also proved effective in rat nerve cells, as well as Parkinson’s patients' cells reprogrammed to become stem cells. The next step beyond testing in cells will be to test the drug in animals and figure out exactly how it works against neurodegenerative diseases. After that, the drug may eventually find its way to the clinic.

And it all started with a novel way of using the lowly yeast.

“These diseases are so difficult,” Lindquist said. “We really need to take every approach we can.”

Josh Sheetz is a junior at the University of North Carolina at Chapel Hill where he studies chemistry. He balances his role as associate editor of Carolina Scientific magazine with his own scientific endeavors in the biochemistry research lab of Henrik Gunnar Dohlman. Reach him at jsheetz@live.unc.edu.