Navigation Links
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 inhibited, reduced the accumulation of toxic fragments associated with HD.

Four of the proteases belong to a family called matrix metalloproteinases (MMP), a class of enzymes already involved in drug development, Dr. Ellerby said. "We've found a target that has known drugs for cancer treatment that could possibly have significance for HD," added Dr. Ellerby. "MMPs are also involved in stroke, inflammation and many neurological processes; we expect a lot of scientific attention to now be focused on this important class of proteases," she said.

Results involving MMPs were verified in mouse models of HD, Dr. Ellerby said. In collaborative studies with Dr. Juan Botas at Baylor College of Medicine in Houston, researchers found that homologs of MMPs suppressed HD-induced neuronal dysfunction in fruit flies. "The next step in this research will be to test some of the MMP inhibitor drugs as a potential treatment in HD mouse models," said Dr. Ellerby. "We'll also be crossing mice that no longer have particular MMPs with those who have HD to see what effect that has on offspring," she said.


'/>"/>

Contact: Kris Rebillot
krebillot@buckinstitute.org
415-209-2080
Buck Institute for Age Research
Source:Eurekalert

Related medicine news :

1. An Earth Day View of Green Building: Earth Advantage Institute Looks 10 Years Forward
2. American Physical Therapy Association (APTA) Kicks Off Social Media Campaign to Help You “Move Forward”
3. University of Colorado Hospital Moving Forward with $400 Million Expansion
4. Gene Therapy for HIV Inches Forward
5. Actor and Humanitarian Harrison Ford Assists Operation Smiles Relief Efforts in Haiti
6. Reliv Foundation Donates $450,000 In Nutritional Supplements to Haitian Relief Efforts
7. Businesses Rally Big Efforts to Benefit the Susan G. Komen Phoenix Affiliates Fight Against Breast Cancer
8. Lighthouse To Help Relief Efforts In Haiti
9. JPMA Supports CPSC Chairman Tenenbaum's Continued Safety Efforts
10. ChildCare Education Institute Supports the First Ladys Efforts to Reduce Childhood Obesity
11. Buildium Announces Fundraising Campaign to Benefit Haiti Relief Efforts
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/8/2016)... ... February 08, 2016 , ... Remember the old saying “rub ... According to Perry A~, author of “Calcium Bentonite Clay” the health benefits of integrating ... balancing and detoxifying the body. , A former motivational speaker, Perry A~ has since ...
(Date:2/8/2016)... ... , ... FileHold's document management software has been implemented by ... environment for FileHold software that is pay per user subscription-based and also does ... FileHold web services API. DocuSyst also advises clients on fully functioning back up ...
(Date:2/8/2016)... ... February 08, 2016 , ... GrassrootsHealth published data from its ... 2 diabetes in the GrassrootsHealth cohort with substantially higher vitamin D levels than ... public health,” states Carole Baggerly, Director of GrassrootsHealth, “the safety and benefits ...
(Date:2/8/2016)... ... , ... TopConsumerReviews.com recently awarded their highest five-star rating to a product from ... a cluster of melanin when exposed to sunlight. Although most moles are benign and ... embarrassment. Historically, mole removal has involved a painful, often expensive visit to ...
(Date:2/8/2016)... NV (PRWEB) , ... February 08, 2016 , ... Guruji ... February 9th, 10th and 11th, 2016 in honor of his birthday on February 10th. ... true happiness. Mahendra Trivedi is known by over 250,000 people from over 40 ...
Breaking Medicine News(10 mins):
(Date:2/8/2016)... Feb. 8, 2016 http://www.researchandmarkets.com/research/x6mkjm/knee ... "Knee Reconstruction Devices Market by Product Type (Primary ... Geography (U.S., Canada, Eu-5, Japan, Bric, Turkey, Indonesia ... report to their offering. --> ... "Knee Reconstruction Devices Market by Product Type ...
(Date:2/8/2016)...  The University of Michigan Health System in ... part of the development of four new operating rooms, ... the U.S. to start using new top-of-the-line neurosurgical imaging ... of neurosurgery. --> Karin Muraszko , ... The BrightMatter technology from Synaptive Medical – a highly ...
(Date:2/8/2016)... DUBLIN , Feb. 8, 2016 /PRNewswire/ ... announced the addition of the "Label-Free ... Global Forecasts to 2020" report to ... has announced the addition of the ... - Global Forecasts to 2020" report ...
Breaking Medicine Technology: