Molecular biologist hopes to learn why degenerative disorder affects specific brain cells

Published on March 27, 2013 at 12:49 AM · No Comments

Dr. Santosh D'Mello, professor of molecular and cell biology at the University of Texas at Dallas, has received a federal grant for research that may shed light on why and how specific brain cells are affected by Huntington's disease, a devastating, degenerative brain disorder.

The grant from the National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health, provides $1.67 million over 5 years.

"Results from our studies could provide valuable insight into why specific brain cells degenerate in Huntington's disease," said D'Mello, who holds appointments in the School of Natural Sciences and Mathematics and the School of Behavioral and Brain Sciences. "I'm pleased with this new grant, particularly given the current funding environment. We're eager to get started on this research."

Huntington's disease is caused by a genetic mutation that is passed down through families. According to the Huntington's Disease Society of America, more than 250,000 Americans have the disease or are at risk of inheriting the disease from an affected parent. The disorder causes parts of the brain to waste away, leading to progressively worsening symptoms ranging from behavioral changes to motor skill impairment to dementia. There is no cure or treatment that can alter the course of the disease.

D'Mello's research, which the NIH has supported for several years, is focused in general on investigating the biological mechanisms underlying neurodegenerative disorders, including Huntington's disease, Alzheimer's, Parkinson's and amyotrophic lateral sclerosis. His recent research results suggest that a key player in promoting neurodegeneration is a protein called histone deacetylase-3 (HDAC3). In preclinical studies, D'Mello's laboratory and other researchers have found that high levels of this protein are toxic to brain cells.

The new grant will allow D'Mello and his research team to investigate possible connections between HDAC3 and Huntington's disease. The genetic mutation responsible for the disorder affects a protein called huntingtin, resulting in a form of the protein that does not function properly. D'Mello will test the hypothesis that the mutant form of huntingtin inherited by patients with Huntington's disease activates the neurotoxic effects of HDAC3 that lead to brain-cell loss.

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