Secretases

Secretases are a class of enzymes that play a crucial role in cellular processes by cleaving proteins. These proteases are membrane-bound and are involved in the shedding of cell surface proteins and the processing of transmembrane proteins. This cleavage can release biologically active fragments from the extracellular domain of a protein, or it can be the first step in the regulated release of peptides from the transmembrane domain.

The most well-studied secretases are members of the ADAM (a disintegrin and metalloproteinase) family and the gamma-secretase complex. ADAMs are involved in a wide range of functions, including cell adhesion, migration, and proteolysis. Gamma-secretase is a multi-subunit enzyme complex that is critical for the processing of the amyloid precursor protein (APP). This processing by gamma-secretase generates amyloid-beta peptides, which are implicated in the pathogenesis of Alzheimer's disease.

Other important secretases include the alpha-secretase and beta-secretase (BACE1) enzymes that also act on APP. Alpha-secretase cleavage typically leads to the production of non-amyloidogenic fragments, while beta-secretase cleavage initiates the amyloidogenic pathway. The precise activity of different secretases on their substrates can determine the fate of the protein and the production of downstream signaling molecules or pathological peptides. The dysregulation of secretase activity is linked to various diseases, making them targets for therapeutic intervention.