Gamma-secretase inhibitorsDo they have a role in the treatment of B-cell lymphoma?

摘要

Gamma secretase inhibitors (GSIs) make up a new class of drugs targeting the Notch signal transduction pathway that are currently in clinical trials for a variety of malignancies and Alzheimer disease. The target of GSIs, y-secretase, is a large multi-protein transmembrane complex composed of presenilin, Aphl, Pen-2 and nicastrin (Fig. I). The role of y-secretase in a variety of physiological and pathological processes is derived from its activity as a protease against Notch, a central molecule in the control of growth and differentiation. gamma-secretase also cleaves amyloid precursor protein, contributing to the generation of the peptide fragments that comprise the amyloid plaques seen in the Alzheimer disease. Notch is a transmembrane protein with an extracellular domain that acts as a receptor for the DSL (Delta, Serrate, lag-2) family of ligands