David Borchelt, Ph.D. • Professor of Neuroscience
College of Medicine

David R. Borchelt’s laboratory is built around the goal of improving understanding of the mechanisms by which the neurodegenerative disease processes diminish the function of neural networks and ultimately cause the death of vulnerable neural cells.

One of the most prevalent neurodegenerative disorders, Alzheimer’s disease, has long been a focus of research in his laboratory. Alzheimer’s disease is widely recognized as the most prevalent type of neurodegenerative disease, characterized by the accumulation of aberrantly folded proteins. These misfolded proteins are seen as both instigators of disease processes and indicators of abnormal protein metabolism. For much of the last several years, Borchelt has worked to unravel the mechanisms that cause mutant proteins to misfold and to determine how the accumulation of such proteins initiates disease.

Borchelt’s most significant work in Alzheimer’s disease includes a study of mice that used state of the art genetic technology to mimic therapeutic approaches to the disease. He demonstrated that amyloid pathology of Alzheimer’s disease is likely to be persistent and difficult to reverse. Borchelt has worked toward identifying therapeutic strategies that could promote repair of the damage caused by Alzheimer’s disease.

Because multiple neurodegenerative disorders are thought to share similar mechanisms of cell injury and toxicity, Borchelt also studies two other neurodegenerative disorders: inherited forms of amyotrophic lateral sclerosis and Huntington’s disease. In both of these disorders, mutations cause the affected protein to acquire aberrant conformations which then causes the protein to self-associate into multimeric complexes within neural cells. By utilizing multiple model systems and by studying multiple neurodegenerative disorders, his laboratory has been at the forefront in looking for common mechanisms that define the molecular events responsible for causing the symptomology of neurodegenerative disorders.

Borchelt’s most recent work focuses on large scale studies of protein metabolism as he pursues the hypothesis that the accumulation of misfolded proteins imposes burden on cellular systems involved in protein metabolism, disrupting the balance between protein synthesis, folding, and protein turnover in a manner that causes global changes in the protein function.