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Gladstone researchers resolve key Huntington's disease mystery in Nature cover story

A mystery long associated with Huntington's disease has been resolved by a team of researchers at the UCSF-affiliated Gladstone Institute of Neurological Disease, thanks to a specially designed microscope that allows researchers to track changes in cells, including those associated with neurodegeneration, over long lengths of time.

As reported in the cover story in the current issue of Nature (Oct. 14, 2004), the team determined that abnormal deposits of mutant huntingtin protein, which appear in the brains of all Huntington's disease patients, aren't the cause of neuronal death. Scientists know that mutant huntingtin protein is responsible for the disease, but they have not known in what form it wreaks its havoc. They haven't known, for instance, whether the abnormal deposits of the protein, known as "inclusion bodies," were, themselves, causative, protective or incidental to the disease. In the current study, the Gladstone team determined that inclusion bodies are a beneficial coping response, possibly sequestering mutant huntingtin protein, thereby reducing levels of the protein elsewhere in the neuron, and thus prolonging neurons' survival.

The finding suggests that mutant huntingtin protein inflicts its damage in some form other than as inclusion bodies, which are insoluble, or resistant to being dissolved in liquid. Investigators may now focus attention on the possibility that the real culprit is a more soluble form of mutant huntingtin spread throughout the neuron, or nerve cell, among other theories.

"We are very excited by these results," says lead investigator Steven Finkbeiner, MD, PhD, an assistant investigator at the Gladstone Institute of Neurological Disease and assistant professor of neurology and physiology at University of California, San Francisco (UCSF). "They will help us to better focus efforts to identify the mechanisms by which the huntingtin protein causes Huntington's and may add to the understanding of other neurode
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Contact: John Watson
jwatson@gladstone.ucsf.edu
415-734-2019
University of California - San Francisco
13-Oct-2004


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