Room 211, Sanders-Brown Center On Aging 800 South Limestone Street Lexington, KY 40536-0230
Molecular and Cellular Biochemistry
Pathogenic mechanisms and treatment of age-related amyloid diseases
My lab is interested in how normal aging, genetics and environment conspire to cause Alzheimer’s disease (AD). The amyloid-β (Aβ) peptide, which deposits in the brain, is believed to cause AD. Our research is based around a working model where we hypothesize that, in most people, AD is caused by a loss of the normal regulation of the two enzymes involved in generating Aβ, β- and γ-secretase (top panel). These enzymes cut Aβ out of a larger membrane protein. In normal individuals, a small amount of Aβ is made as a byproduct of normal cellular metabolism. Cells secrete the peptide, and it is then degraded. In AD, a variety of things cause β- and γ-secretase to become more active. This leads to the generation of more Aβ, which overwhelms the brain’s clearance capacity. This eventually leads to disease. We use a variety of methods in cellular and molecular biology to understand why this happens, in the hope that this will one day lead to effective treatments.