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Parkinson’s Damage Under Scrutiny ...

Thursday December 18, 2003

2003/12/14 00:03:23 (The BBC News ) - Scientists May Be Able To Use Simple Baker’s Yeast To Recreate The Destruction Wreaked By Parkinson’s Disease In A Test Tube. US researchers overloaded yeast cells with a body chemical implicated in the human disease - then watched as Parkinson- like damage emerged. It is hoped that the experiments will help them devise ways to halt the disease in its tracks. The yeast model could now be used for early tests of promising treatments. Scientists believe that Parkinson’s patients have a problem in the brain caused by a "protein" called alpha-synuclein (aSyn). Even in small amounts, this protein can persuade nearby brain proteins to lose their normal shape and form irregular clusters. The shape of a protein is vital to its proper function, and the clusters appear eventually to cause brain cell death, leading to the characteristic symptoms of Parkinson’s - progressively worsening tremor and muscle rigidity.

There are drug treatments which can ease these, but over time they lose their effectiveness, and there is no complete cure for the condition. Doctors cannot simply start looking at manipulating the brains of live human patients to see what is going on, and need a cheap alternative which would allow them to test new theories swiftly. Yeast cells may offer an alternative. The researchers, from the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, assembled a group of yeast cells, each manipulated to carry differing amounts of aSyn protein. Tiago Outeiro, one of the team, said: "Basically, I wanted to see what happens in the cell when we produce just a bit more that the quality-control system can handle.”Does the biology of the protein change? Does it simply sit there? Does it cause problems to the cell?"

They observed that aSyn at low levels in the cell appeared to play a perfectly legitimate role - heading for the cell membrane and regulating the processing of fats. But as the levels of aSyn rose, problems began to arise. Some of the proteins "misfolded", forming the wrong shape, and caused other nearby proteins to do the same thing. These proteins gathered into clusters, and the cell began to die.

Redressing the balance Professor Susan Lindquist, another Whitehead researcher, said the implications were important. "This confirms our suspicions that many of these proteins that cause disease can be very finely balanced, and when you tip the balance over just a little bit, it doesn’t take a whole lot to cause a reaction.

"But the hopeful thing is that it might not take a whole lot to tip the balance back, by devising ways to improve the quality control mechanisms in cells that normally dispose of these misfolded proteins."

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