Project Details
Beta‐amyloid, the sticky protein that is the main component of brain plaques in Alzheimer's disease, is created by clipping it from a bigger protein, called beta‐amyloid precursor protein (APP). This clipping of APP is done by gamma secretase, a bundle of proteins that includes presenilin 1 or 2, APH‐1, PEN‐2, and nicastrin (NCT). NCT is the part of the bundle that recognizes and pulls into the complex many of the proteins, including APP, that are then processed by the rest of the gamma secretase proteins. Drs. Sangram Sisodia, Shohei Koide, and collaborators will study the shape of NCT to better understand how it partners with other proteins. They will make antibodies that bind like a lock and key to different parts of NCT to aid in their analysis. Once the shape of NCT is determined, the next step will be to design and test new drugs to specifically block NCT from binding to APP and, as a result, prevent the creation of beta‐amyloid.