Huntington’s disease is cruel and devastating. The inherited disorder’s signature is the wasting away of brain nerve cells, leading to a host of nightmarish symptoms and outcomes. In Huntington’s, a portion of DNA known as a CAG repeat occurs 30 to 120 times rather than the 10 to 28 times that it does in normal cells. As the gene passes through families, the CAG repeats often get longer, hastening the development of disease at increasingly younger ages. Symptoms include uncontrolled movements, fidgeting, hallucinations, paranoia and dementia. One in 10,000 people of European stock is affected by Huntington’s. There is no cure, and while some drugs show promise, no known way exists to prevent the disease from getting worse.
Rohit Pappu, PhD, professor of biomedical engineering and director of the new Center for Biological Systems Engineering, studies proteins involved in the development of Huntington’s disease and related neurodegenerative motor control disorders. All involve an ensemble of recently recognized eccentric proteins, known as intrinsically disordered proteins (IDPs), and share the common theme of protein aggregation, or clumping, leading to neuronal death and disease. Perhaps the best-known example of protein aggregation is the beta amyloid plaques seen in the brains of Alzheimer’s disease patients.
IDPs comprise approximately one-third of proteins the human body draws upon to perform its myriad functions and carry out the dictates of its genes. Within the past 10 years, a consensus formed among a group of scientists that these proteins did not have a single, predictable structure.
Researchers found instead that proteins shift their shapes, organize networks of other proteins, are relevant to biological complexity — giving rise to higher function in us humans (and distinguishing us from other species) — and also promote disease, lots of disease.
IDPs have been implicated in cancers, cardiovascular diseases and a whole range of neurodegenerative disorders, including Parkinson’s disease, Alzheimer’s (AD), Huntington’s, groups of brain ataxias and a form of muscular dystrophy.
Organizing a network himself, Pappu in the past year has helped assemble a group of eight researchers, located on the second floor of Brauer Hall on the Danforth Campus. Each is devoted to an area of biomedical science with the common goal of understanding the essence of biomolecular and cellular networks.
Read more on magazine.wustl.edu.
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