Amyloid-beta precursor protein secretase

Secretases are enzymes that "snip" pieces off a longer protein that is embedded in the cell membrane.

[citation needed] Sequential cleavage by beta-secretase 1 (BACE) and gamma-secretase (γ-secretase) produces the amyloid-beta peptide fragment that aggregates into clumps called amyloid plaques in the brains affected by Alzheimer's disease.

[1] If alpha-secretase (α-secretase) acts on APP first instead of BACE, no amyloid beta is formed because α-secretase recognizes a target protein sequence closer to the cell surface than BACE.

γ-secretase plays a critical role in developmental signalling by the transmembrane receptor Notch, freeing the cytoplasmic tail of Notch to travel to the cell nucleus to act as a transcription factor.

Although BACE cleaves the extracellular domains of several transmembrane proteins, its physiological function remains unknown.