Gamma secretase is an intramembrane protease that cleaves several substrates, including the Notch receptor and the amyloid precursor protein (APP). The cleavage of the Notch receptor results in the release of the Notch intracellular domain (NICD), which translocates to the nucleus and regulates gene expression. By inhibiting gamma secretase, GSIs prevent the release of NICD, thereby disrupting Notch signaling and potentially impeding tumor growth and survival.
