Four proteins comprise the gamma-secretase complex: presenilin, nicastrin, aph-1, and PEN-2. Together, these proteins mediate cell surface signaling pathways for a variety of type I membrane proteins, notably amyloid-beta precursor protein, a protein implicated in the development of Alzheimer's disease, via intramembrane proteolysis. The proteins assemble into a proteolytically active complex in the golgi/trans-golgi network (TGN) compartments. Assembly leads to autocleavage of presenilin into two subunits to create the active site of gamma-secretase, an important step in understanding the mechanisms involved in the etiology and possible treatment of Alzheimer's disease.
