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Overexcited neurons not good for cell health
Date:12/17/2007

EVANSTON, Ill. --- Neurotransmitters have consequences. They initiate events that are critical to a healthy life, giving us the ability to move, to talk, to breathe, to think. But thats if the neurotransmitters are getting it right and sending proper signals downstream to muscle cells, neurons or other cells.

Now a Northwestern University study reports that a mutation in a transcription factor that controls a neurotransmitter in the nematode C. elegans causes an imbalance in neuronal signaling that results in protein damage in target cells. Similar results and consequences on protein folding were found to occur upon exposure to the common toxins nicotine and lindane (a pesticide).

Whether due to genetic mutation or exposure to small molecules, the neurons become overexcited and fire incorrect signals too rapidly, resulting in proteins in target muscle cells becoming stressed, misfolding and becoming non-functional.

To find that small molecules reproduce our genetic observations -- that both environment and genetics cause a molecular defect in the ability of proteins to function in muscle cells -- was not expected, said Richard I. Morimoto, Bill and Gayle Cook Professor of Biochemistry, Molecular Biology and Cell Biology in Northwesterns Weinberg College of Arts and Sciences, who led the research team.

This study provides some of the strongest evidence that nerve cell activity can directly affect the protein folding process in another cell. (Muscle cells in the case of this study.) Many different diseases and conditions, such as many neurodegenerative diseases, certain cancers, muscular dystrophy and the aging process, cause loss of muscle cell function. How that happens is not well understood.

We may have discovered an unexpected basis for a number of human diseases, said Morimoto. Particularly interesting is the link with the environment. Weve shown that pesticides, which are widespread and have been linked to an
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Contact: Megan Fellman
fellman@northwestern.edu
847-491-3115
Northwestern University
Source:Eurekalert

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