Identifying Pathways In The Brain To Understand The Underlying Molecular Mechanism Of Huntington's Disease

Main Category: Huntingtons Disease
Also Included In: Neurology / Neuroscience;  Biology / Biochemistry
Article Date: 21 May 2009 - 2:00 PDT

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Florida Atlantic University researcher Dr. Jianning Wei, assistant professor of biomedical sciences in the Charles E. Schmidt College of Biomedical Science at FAU, has received a grant from the National Institutes of Health (NIH) to further her research into the molecular mechanisms of Huntington's disease (HD). Named after American physician George Huntington, HD is a highly complex genetic, neurological disorder that causes certain nerve cells in the brain to waste away. The disease, characterized by a selective loss of neurons in the brain, affects the basal ganglia, which controls motor control, cognition, learning and emotions. It also affects the outer surface of the brain, or the cortex which controls thought, perception, and memory. Wei and her colleagues are working to identify the pathways in the brain that are altered in response to mutant proteins, as well as to understand the cellular processes impacted by the disease in order to facilitate the development of effective pharmacological interventions.

HD is a fatal, inherited disease caused by abnormal repeats of a small segment in an individual's DNA, or genetic code. The production of malfunctioning proteins in the body are results of these mutations, and the more it is repeated, the worse the disease. A person who has the disease carries one normal copy of the gene and one mutated copy in his or her cells. These abnormal repeats also are involved in several other neurodegenerative diseases. Although the mutated forms of these genes are known for their devastating effects, their normal forms are critical for nerve function, embryonic development and other bodily processes.

"The underlying molecular mechanism of HD remains elusive," said Wei. "We hope that the information we obtain from our studies will improve the current understanding of the molecular pathways that are altered in response to mutant huntingtin or mHtt."

Wei's findings may also represent a universal mechanism in the pathogenesis of neurodegenerative diseases that are involved with protein misfolding and aggregation (a phenomenon that occurs in many highly debilitating disorders including neurodegenerative diseases). Preliminary data from their findings using an in vitro cell model of HD suggest that there is a novel mechanism for mHtt induced cell death, or apoptosis. Apoptosis has been proposed as one of the mechanisms leading to neuronal death in HD. With this NIH grant, Wei and her colleagues will be testing their hypothesis in a mouse model of HD. Although recent studies provide important clues, precisely how mHtt triggers apoptosis still remains unclear.

HD can be traced back as far as the Middle Ages and one of the earlier names for the disease was "chorea" as in "choreography" and is the Greek word for dance, describing how people affected with the disorder constantly twist and turn in an uncontrollable dance-like motion. People are born with the single defective gene that produces HD and symptoms don't appear until middle age. In addition to uncontrolled movements, neurological degeneration also causes loss of intellectual faculties and emotional disturbance. As the disease progresses, HD can affect a person's ability to walk, talk and swallow.

Today, approximately 30,000 Americans are living with HD. In addition, a staggering 200,000 more are at risk. Although physicians may prescribe a number of medications to help control emotional and movement problems associated with HD, there is no treatment to stop or reverse the course of the disease.

Current investigation of HD includes clinical research, basic neurobiology, imaging, fetal tissue research and animal models of the disease.

Florida Atlantic University opened its doors in 1964 as the fifth public university in Florida. Today, the University serves more than 26,000 undergraduate and graduate students on seven campuses strategically located along 150 miles of Florida's southeastern coastline. Building on its rich tradition as a teaching university, with a world-class faculty, FAU hosts ten colleges: College of Architecture, Urban & Public Affairs, Dorothy F. Schmidt College of Arts & Letters, the Charles E. Schmidt College of Biomedical Science, the Barry Kaye College of Business, the College of Education, the College of Engineering & Computer Science, the Harriet L. Wilkes Honors College, the Graduate College, the Christine E. Lynn College of Nursing and the Charles E. Schmidt College of Science.

Source: Florida Atlantic University