Huntington’s disease, a debilitating brain disorder that impacts movement and typically results in death within 20 years of its onset, affects more than a quarter of a million of Americans.
Researchers at West Virginia University are trying to understand mechanisms underlying the build-up of the huntingtin protein in the brain associated with the disease for answers that could unlock avenues for more effective medical treatment.
The disease is caused by a sequence in the huntingtin gene that encodes an abnormally long repeat of the amino acid glutamine, which in turn leads to the build-up of protein clumps within neurons that are associated with the disease.
A research team led by Justin Legleiter, associate professor in the C. Eugene Bennett Department of Chemistry West Virginia University is studying the 17 amino acid-long sequence that can be found directly adjacent to the abnormality.
Recent research in the field has shown that the sequence, commonly referred to as N17, plays an important role in modifying huntingtin protein accumulation and potentially the development of Huntington’s disease. Important for this specific study, N17 is also known to facilitate the binding of the protein to cellular membranes.
“We don’t have a completely clear picture, but there’s evidence that there may be key interactions between huntingtin and a variety of cellular membranes that are predominately composed of lipids,” Legleiter said.
Legleiter is using a grant from the National Institutes of Health to determine how modifications to theN17 sequence can regulate the interaction of the huntingtin protein with specific types of lipid membranes, which may play a role in Huntington’s disease.
Once the team interprets details of huntingtin’s interaction with membranes, this knowledge could lead to new therapeutic targets for discovering new drugs to combat the disease that places more than 250,000 Americans at risk.
Huntington’s disease, which is incurable, is an inherited condition that results in uncontrollable movement, dementia and ultimately death. It can be passed down through families even if only one parent is a carrier of the abnormal huntingtin gene.
Source: West Virginia University