Sunday, May 5, 2024
5/5/2024
Alzheimer’s disease (AD), a progressive neurodegenerative disease and leading cause of dementia, exacts a tremendous toll on both the healthcare system and society broadly. Although the pathogenesis of AD is poorly understood, it centers on the production of so-called ß-amyloid (Aß) peptides, which are produced from amyloid precursor protein (APP) by the intramembrane protease ¿-secretase. Indeed, mutations in the catalytic subunit of ¿-secretase alter Aß production profile and cause familial AD, making the protease a promising target for developing therapies to treat or prevent Alzheimer’s Disease. Specifically, developing agents that can modify ¿- secretase activity to selectively reduce the formation of pathogenic ß-amyloid species without affecting ¿- secretase’s overall activity represent an attractive strategy to target AD. Despite significant progress in studying ¿-secretase, we still do not understand how its catalytic activity and specificity are modulated at a mechanistic level. In the proposed project, we will apply a new approach and leverage novel reagents to investigate ¿- secretase and its modulation. Using an interdisciplinary approach, we aim to elucidate how the cellular context and external factors modulate ¿-secretase at the molecular level. We will also characterize new tools and reagents for ¿-secretase and define their mechanism of actions. Collectively, the proposed studies will provide much needed insights into ¿-secretase modulation and offer a molecular basis for Alzheimer’s disease pathogenesis and therapeutic development.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).
