Gamma-secretase substrate (None)

"Gamma-secretase substrate" is a generic descriptor for any protein that is recognized and cleaved within its transmembrane domain by the gamma-secretase protease complex. This diverse set of substrates are predominantly type I transmembrane proteins that first undergo extracellular domain shedding before being cleaved by gamma-secretase inside the lipid bilayer. The two most extensively characterized substrates are amyloid precursor protein (APP), whose cleavage generates amyloid-beta peptides implicated in Alzheimer's disease, and Notch, a cell-surface receptor central to cell fate determination and cancer. Over 90 substrates have been documented, contributing to gamma-secretase's role in multiple signaling and regulatory pathways. Drugs targeting gamma-secretase affect all its substrates, giving rise to therapeutic challenges due to the pleiotropic functions and broad substrate spectrum of the enzyme[1][2][3][8].

Other names

Gamma-secretase target proteinsSubstrates of gamma-secretaseNone that refer to a single molecule

Gamma-secretase inhibitors act by binding to the gamma-secretase complex, thereby inhibiting the proteolytic cleavage of all its substrates. Modulators may alter substrate specificity or cleavage efficiency, affecting the processing of different substrates to varying degrees.