Beta-secretase (BACE) is an aspartic-acid protease important in the formation of myelin sheaths in peripheral nerve cells. The transmembrane protein contains two active site aspartate residues in its extracellular protein domain and may function as a dimer. BACE1, as also β-site amyloid precursor protein cleaving enzyme 1, is an aspartic protease, which is a family of protease enzymes that use an aspartate residue for the catalysis of their substrates. BACE2 is a homologue of BACE1 that is mapped to the DS critical region. BACE2, however, does not appear to be the major beta-secretase and cannot compensate for loss of BACE function. BACE may be an important new therapeutic target for treatment of Alzheimer's disease.
Alzheimer's disease (AD) is caused by aggregates of the amyloid-β, which is generated by cleavage of the amyloid precursor protein (APP) by beta-secretase (BACE-1) followed by gamma-secretase. The beta amyloid (Aβ) is generated by two enzymes which cut APP at two different positions: β-secretase cuts APP at a position outside the cell and γ-secretase which cuts APP at a position inside the cell membrane.