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Leap forward in efforts to develop treatments for Huntington's disease
Date:7/28/2010

Scientists at the Buck Institute for Age Research have discovered that a particular family of enzymes are involved in the breakdown of proteins that modify the production of toxic fragments that lead to the pathology of Huntington's disease. These enzymes, matrix metalloproteinases (MMPs), provide new targets for drug therapies for the disease targets that have already been shown to respond to cancer drugs currently in clinical development. Results of the research, from the laboratories of Buck faculty members Lisa Ellerby, Ph.D. and Robert Hughes, Ph.D., appear as the cover story in the July 29, 2010 edition of Neuron.

Huntington's disease (HD) is an incurable progressive neurodegenerative genetic disorder which affects motor coordination and leads to cognitive decline and dementia. Symptoms usually begin to occur in middle age; patients are often totally incapacitated prior to death. The worldwide prevalence of HD is 5-10 cases per 100,000 people; the rate of occurrence is highest in peoples of Western European descent.

The disease stems from a mutation in the huntingtin gene, located on human chromosome four. The mutation causes abnormalities in the huntingtin protein (mutantHtt, or mHtt). The pathology of HD is accelerated when mHtt is cut into smaller, highly toxic fragments via various molecular activities. Dr. Ellerby said to date, scientific queries into how those fragments are cut have focused primarily on caspases, a family of intracellular proteins that mediate cell death, and calpains, enzymes regulated by the concentration of calcium ions. The Buck Institute study involved proteases, various enzymes that catalyze the breakdown of proteins in reaction to water. Dr. Ellerby said this research marks the first time all of the 514 different types of proteases found in humans were individually screened in cell culture to see how they affect mHtt proteolysis. Buck Institute researchers identified 11 proteases that, when inhibi
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Contact: Kris Rebillot
krebillot@buckinstitute.org
415-209-2080
Buck Institute for Age Research
Source:Eurekalert

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