Yeast Gives Clues To Parkinson's

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Main Category: Parkinson's Disease
Also Included In: Genetics;  Biology / Biochemistry
Article Date: 27 Feb 2009 - 11:00 PDT

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Scientists from the US and Australia are using cells from yeast and mammals to learn about how environment and genes affect whether a person gets Parkinson's disease or not.

Many aspects of the way yeast cells work are the same in animal and human cells, and since it is only possible to get hold of cells diseased with Parkinson's after a person is dead, having a similar more easily accessible cell to work with helps scientists study the early development of the disease and scan and test the thousands of genes that might be involved.

One such example is the subject of a study published this week in Nature Genetics, where Antony Cooper from Sydney's Garvan Institute of Medical Research in Australia and colleagues have for the first time found a way to connect three pieces of the Parkinson's disease jigsaw: sensitivity to manganese, and the behaviour of two genes, alpha-synuclein and PARK9 (also known as ATP13A2).

Alpha-synuclein and PARK9 have already been separately associated with forms of Parkinson's, and manganese poisoning can cause Parkinson-like symptoms in miners and welders exposed to high levels of the metal.

Parkinson's disease is where neurons that produce the neurotransmitter dopamine degenerate, and scientists have also known for some time that this is associated with an overexpression of the protein alpha-synuclein which autopsies have found in abundance in affected regions of the brain.

A European team also previously found that PARK9, already known to be involved in a hereditary form of Parkinson's, was in much greater abundance in the brains of people who had died of sporadic (ie not inherited) forms of the disease compared to the same parts of the brain in people who did not have the disease.

Cooper suspects that PARK9 was actually protecting the neurons and may explain why many of them surrounded by PARK9 survived.

What Cooper and colleagues found was that PARK9 appears also to diminish the toxic effects of alpha-synuclein, and it may also act as a manganese pump that is potentially capable of removing excess amounts of the metal from cells.

Cooper and colleagues were able to study the effect of PARK9 in yeast because it contains an equivalent gene.

An important and puzzling question in Parkinson's research is whether there is a single or cluster of genetic factors that cause the degeneration of neurons that produce dopamine.

As Cooper explained:

"We would love to be able to link all the genes that we know have something to do with Parkinson's disease."

"If you discover there's a central pathway involved, it provides much better potential for finding a successful treatment," he added, explaining that so far they have linked PARK9, alpha-synuclein and manganese, and this is no coincidence.

"They're likely to be affecting a pathway and we suspect it's a central pathway. To confirm that would be very exciting indeed," said Cooper.

Cooper has been working for some years, with co-authors Dr Susan Lindquist, from the Whitehead Institute for Biomedical Research and Dr Aaron Gitler, from the University of Pennsylvania School of Medicine, to find how alpha-synuclein might cause cell damage.

They teamed up with associate professor Guy Caldwell, of the University of Alabama, and associate professor Jean-Christophe Rochet from the University of Purdue in Indiana, to check their results using other models of Parkinson's disease.

The more models the findings fit into, the more you are likely to believe them, said Cooper.

"Alpha-Synuclein is part of a diverse and highly conserved interaction network that includes PARK9 and manganese toxicity."
Aaron D Gitler, Alessandra Chesi, Melissa L Geddie, Katherine E Strathearn, Shusei Hamamichi, Kathryn J Hill, Kim A Caldwell, Guy A Caldwell, Antony A Cooper, Jean-Christophe Rochet and Susan Lindquist.
Nature Genetics 41, 308 - 315, Published online: 1 February 2009.
doi:10.1038/ng.300

Click here for Abstract.

Sources: Journal abstract, Research Australia.

Written by: Catharine Paddock, PhD
Copyright: Medical News Today
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