{{Short description|Type of enzyme}}{{More citations needed|date=June 2024}}thumb|300px|right|Processing of the amyloid-beta precursor protein'''Secretases''' are enzymes that "snip" pieces off a longer protein that is embedded in the cell membrane.

Among other roles in the cell, secretases act on the amyloid-beta precursor protein (APP) to cleave the protein into three fragments.{{Citation needed|date=June 2024}} 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.<ref>{{Cite journal |last=Bhatia |first=S. |date=12 August 2023 |title=Scaffold Morphing and In Silico Design of Potential BACE-1 (β-Secretase) Inhibitors: A Hope for a Newer Dawn in Anti-Alzheimer Therapeutics |journal=Molecules |location=Basel, Switzerland |volume=28 |issue=16 |page=6032 |doi=10.3390/molecules28166032|doi-access=free |pmid=37630283 |pmc=10459662 }}</ref> 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. The non-pathogenic middle fragment formed by an α/γ cleavage sequence is called P3.{{citation needed|date=June 2021}}

==Structure== The structure of the three secretases varies widely.

* The α-secretase gene has not been conclusively identified but is believed to be a metalloproteinase. * BACE is a transmembrane protein with an extracellular aspartic acid protease domain. * γ-secretase is actually a protein complex containing presenilin, nicastrin, APH-1, and PEN-2. Presenilin is believed to harbor the protease domain and represents an important example of an uncommon type of protease that cleaves targets within the cell membrane.

==Function== Besides their involvement in the pathogenesis of Alzheimer's, these proteins also have other functional roles in the cell.

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.

==References== {{Reflist}}

==External links== * {{MeshName|Secretase}}

{{Proteases}}

Category:Enzymes Category:Integral membrane proteins