{{Short description|Type of enzyme}}{{More citations needed|date=June 2024}}[[image:APP processing.png|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 (biology)|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 [[brain]]s 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 [[protein structure|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]] [[Protein domain|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 [[signal transduction|developmental signalling]] by the [[transmembrane receptor]] [[Notch signaling|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]]