Too Much of a Good Thing


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A major feature of Parkinson's disease, the brain disorder that causes muscle tremors, stiffness and weakness, is a shortage of the signal molecule dopamine in the brain. A new Weizmann Institute study now confirms the prevalent theory that this shortage results from dopamine's own destructive activity.

The research, conducted on human nerve cells by Prof. Rabi Simantov of the Molecular Genetics Department and reported in Neuroscience, may also explain why L-dopa, a drug commonly used against Parkinson's, often ceases to be effective after a while.

Dopamine is a chemical messenger that allows brain cells to communicate by relaying electrical signals between their nerve endings. The quantity of such essential messengers affects the quality of cell communication: Too little slows and weakens it.

However, too much can amplify the cellular signal to a level that causes abnormal behavior and the death of nerve cells. Simantov showed that this is precisely what can happen with human dopamine-producing cells.

He demonstrated in tissue culture that an abnormal increase in the amount of dopamine in the spaces between the cells causes these cells to commit suicide.

This finding supports the notion that in Parkinson's, a continued and uncontrolled rise in the amount of dopamine may gradually lead to the death of dopamine-producing cells. This, in turn, reduces the amount of dopamine in the brain and significantly weakens the cellular communication signals.

Likewise, the effects of L-dopa may wear off if the drug, which the body converts into dopamine, causes the death of dopamine-producing cells. Scientists believe that clarification of these cellular processes points the way to the development of new methods to block Parkinson's disease.

Prof. Simantov holds the Andre Lwoff Chair of Neurogenetics. His team included graduate students and associates Helena Blinder, Shai Porat, Miriam Tauber, Dr. Mordechai Gabbay and Gustavo Tafet. Funding for this research was provided by the Israel Ministry of Health and the Israel Antidrug Authority, as well as the Mella and Leon Benoziyo Center for Neurosciences, the Leo and Julia Forchheimer Center for Molecular Genetics and the Murray H. and Meyer Grodetsky Center for Research of Higher Brain Functions at the Weizmann Institute.

The Weizmann Institute of Science is a major center of scientific research and graduate study located in Rehovot, Israel.