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Penn study finds link between Parkinson's disease genes and manganese poisoning
Date:2/1/2009

PHILADELPHIA A connection between genetic and environmental causes of Parkinson's disease has been discovered by a research team led by Aaron D. Gitler, PhD, Assistant Professor in the Department of Cell and Developmental Biology at the University of Pennsylvania School of Medicine. Gitler and colleagues found a genetic interaction between two Parkinson's disease genes (alpha-synuclein and PARK9) and determined that the PARK9 protein can protect cells from manganese poisoning, which is an environmental risk factor for a Parkinson's disease-like syndrome. The findings appear online this week in Nature Genetics.

Manganism, or manganese poisoning, is prevalent in such occupations as mining, welding, and steel manufacturing. It is caused by exposure to excessive levels of the metal manganese, which attacks the central nervous system, producing motor and dementia symptoms that resemble Parkinson's disease.

In Parkinson's patients, the alpha-synuclein protein normally found in the brain misfolds, forming clumps. Yeast cells, the model system in which Gitler studies disease proteins, also form clumps and die when this protein is expressed at high levels. These are the same yeast cells that bakers and brewers use to make bread, beer, and wine.

As a postdoctoral fellow at the Whitehead Institute in Cambridge, Massachusetts, Gitler and colleagues started looking for genes that could prevent the cell death caused by mis-folded alpha-synuclein in yeast. Eventually they found a few genes to test in animal models and some were able to protect neurons from the toxic effects of alpha-synuclein. "One of the genes that we found was a previously uncharacterized yeast gene called YOR291W. No one knew what it did back in 2006," he recalls.

In the meantime, researchers in Europe published studies about a family that had an early-onset form of a type of Parkinson's disease caused by mutations in the PARK9 gene. "When I read about this study
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert  

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