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Posted: September 16, 2008

Parkinson's Disease Appears to Respond to Baker's Yeast Protein

A protein in baker’s yeast has been found in animal trials to protect against Parkinson’s disease by preventing the tell-tale protein clumping that leads to nerve cell death that is characteristic of the degenerative motor disorder.

By introducing the yeast protein Hsp104 into animal models of Parkinson's disease, researchers at the University of Pennsylvania School of Medicine prevented the worrisome protein clumping. Their findings were published in the Journal of Clinical Investigation.

"Yeast expresses a protein called Hsp104, which is able to reverse protein aggregation," says James Shorter, PhD, assistant professor of biochemistry and biophysics at Penn. "However, for reasons that are unclear, Hsp104 is not found in mammals. We wondered if introducing Hsp104 into mammals could help with diseases connected with protein aggregation."

Clinicians do not fully understand the process or cause of Parkinson's disease, which afflicts more than a million Americans, with no treatments currently available that fundamentally alter the course of the condition.

However, researchers believe that a protein called alpha-synuclein mis-folds and clumps in many forms of the disease, and that this process is intimately tied to the selective death of dopamine-producing neurons that breeds Parkinson's.

In this study, Penn researchers found that Hsp104 could partially reverse alpha-synuclein aggregation in test-tube experiments. Remarkably, they said, rats expressing Hsp104 showed lower levels of alpha-synuclein aggregation and alpha-synuclein-induced toxicity of neurons.

The research team said this outcome is significant because the rat model they used recreates the selective loss of dopamine-producing nerve cells in the region of the brain affected in Parkinson’s.

"This study represents an important preliminary step," says Shorter. "One thing we'd like to do next is to treat an animal model which already has considerable quantities of alpha-synuclein aggregates to see if Hsp104 can actually reverse the process in the rat brain."

The Michael J. Fox Foundation, European Molecular Biology Organization, Swedish Parkinson's Foundation, Swiss National Science Foundation, American Heart Association, University of Pennsylvania Institute on Aging, and the National Institute of Health Director's New Innovator Award provided funding for this research.

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