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Protein Linked to Parkinson’s

June 2, 2002

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WASHINGTON (AP) _ A protein that exists normally in most of the cells in the brain has been identified as a possible factor in the development of Parkinson’s disease _ a finding that could point the way to treatments but raise questions about current therapy.

In lab experiments, when the brain protein alpha-synuclein combines with dopamine in nerve cells it can trigger the production of toxic reactive oxygen molecules that kill the nerves, according to a research team led by Dr. Bruce A. Yankner of Harvard Medical School.

If this process operates in patients the same way it does in the laboratory, it could set scientists on the path to potential treatments, Yankner said.

But it also adds to the debate over whether the current use of dopamine in the treatment of Parkinson’s could make things worse in the long run, he added.

The findings appear in the June issue of the journal Nature Medicine.

Dr. Ronald Lee Hamilton of the University of Pittsburgh called the research ``a significant advance, but not a major breakthrough.″

``It does not address the question of why alpha-synuclein accumulates in these neurons, but it does provide a potential mechanism by which these neurons might die,″ he said.

Dr. Robert E. Burke of Columbia University said the study ``adds to the growing body of information which is pointing toward the importance of synuclein’s role in affecting the viability of dopamine neurons.″

Neither Hamilton nor Burke was connected with the research team.

More than a million Americans are victims of Parkinson’s, which causes muscle stiffness and tremor as neurons in the brain are damaged. The disease has received widespread attention due to several prominent patients, including former Attorney General Janet Reno, boxing champion Muhammad Ali and actor Michael J. Fox.

Alpha-synuclein is present in most cells in the brain and its normal function is not entirely clear, Yankner said in a telephone interview. It may have a protective function against certain stresses, he said.

In Parkinson’s disease there are lesions on the nerve cells that turn out to be made of alpha-synuclein and other chemicals,, he said. In addition, some families with a mutated form of alpha-synuclein have a tendency to develop Parkinson’s.

``That says that when something goes wrong with this protein, that’s enough to cause Parkinson’s disease. That’s a smoking gun,″ Yankner said.

``If it turns out that this theoretical framework that we’ve shown in the laboratory is actually operative in the patient,″ scientists could try several approaches to treating the disease, he said.

These could include finding ways to prevent alpha-synuclein from combining with other proteins also involved in the process, preventing it from accumulating in nerve cells or keeping it away from dopamine.

Meanwhile, however, one of the main approaches to dealing with the symptoms is treating patients with dopamine, a process that seems to work at least in the short term.

There can be side effects to this treatment and it isn’t used for long periods, Yankner said.

``This has been a question for a while,″ he said, whether dopamine, while temporarily making things better might, over the long run, make things worse.

``Our paper doesn’t address that,″ he said, adding that animal studies are under way to answer that question.

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