Cell Stress May Contribute to Neurological Diseases

Release Date:
4/16/2004
Contact:
NIGMS OCPL
301-496-7301
info@nigms.nih.gov

People respond to stress or heat by sweating; cells respond by activating heat shock proteins that help repair or clear damaged proteins. Research by cell biologist William Welch, Ph.D., of the University of California, San Francisco, has illuminated an important connection between heat shock proteins and nine devastating neurological diseases, including Huntington's disease.

Scientists know that all of the diseases are associated with mutant proteins that form clumps in nerve cells, leading to the cells' death. Welch used mouse cells to study one of these diseases, spinobulbar muscular atrophy (SBMA). In SBMA, clumping of the mutated proteins activates the cell's stress response system, generating heat shock proteins that would normally rid the cell of the malformed proteins. Welch found that the protein clumps grab the heat shock proteins before they can do their work, permanently activating the stress response system. This generates still more heat shock proteins, which are in turn pulled out of commission by the clumps.

In addition, Welch discovered that cells damaged in this way are extremely sensitive to various kinds of stress, including heat and different toxins. His experiments showed that only half of the cells with the clumped proteins survived a temperature increase that normal cells could tolerate. Moreover, the abnormal cells that did survive experienced further clumping. These results suggest that physiological or environmental stress may play a role in initiating and/or accelerating this group of neurological diseases. Welch is now using laboratory mice to test whether stressed animals do indeed develop more quickly than do non-stressed animals.

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