What does a secretase do?
What does a secretase do?
Secretases represent a diverse group of proteases that cleave membrane proteins in a limited manner. Their substrates are membrane bound and the limited cleavage may be enforced by the release of large products from the membrane after initial endoproteolysis.
What does alpha-secretase produce?
α-Secretase cleaves within the Aβ peptide sequence region of APP, breaking the lysine 16 and leucine 17 peptide bond, to produce sAPPα and the membrane-tethered C83, which is subsequently processed by γ-secretase to produce p3 and AICD (Esch et al., 1990; Anderson et al., 1991; Wang et al., 1991).
What is the main role of secretase proteases?
Three proteases that are involved in the processing of amyloid precursor protein—α-secretase, β-secretase and γ-secretase—are of particular interest as they are central to the generation and modulation of amyloid-β peptide and can be targeted by small compounds in vitro and in vivo.
Where is alpha-secretase located?
cell membrane
Alpha secretases are members of the ADAM (‘a disintegrin and metalloprotease domain’) family, which are expressed on the surfaces of cells and anchored in the cell membrane. Several such proteins, notably ADAM10, have been identified as possessing alpha-secretase activity.
What secretase inhibitors?
Secretases inhibitors are important agents that inhibit the development of senile plaques. β-secretase (BACE) inhibitors are in lime light for the drug development of AD. BACE initiates the production of Aβ, so its inhibition provides a valid target for the AD.
How does APP cause Alzheimer’s disease?
The amyloid precursor protein (APP) is pivotal in the pathophysiology of Alzheimer’s disease since its abnormal cleavage by β-secretase and γ-secretase generates β-amyloid peptide, which aggregates into neurotoxic amyloid plaques in the brain tissues.
How does gamma secretase work?
With more than 90 known substrates, the γ-secretase complex is considered “the proteasome of the membrane”, with central roles in biology and medicine. The protease carries out hydrolysis within the lipid bilayer to cleave the transmembrane domain of the substrate multiple times before releasing secreted products.
Where is tau protein from?
The tau protein is predominantly found in brain cells (neurons). Among tau’s multiple functions in healthy brain cells, a very important one is stabilization of the internal microtubules. Tau is a small protein with a short name but a large reputation because of its association with multiple brain diseases.
How do gamma secretase inhibitors work?
Gamma secretase inhibitors (GSIs) are a class of drugs that gained attention during the past decade in cancer treatment. The use of GSIs for cancers is primarily based on the premise that GSIs act by inhibiting the cleavage of γ-secretase, which result in blocking Notch 1 signaling [272].
Where is APP found in the body?
Normal Function. The APP gene provides instructions for making a protein called amyloid precursor protein. This protein is found in many tissues and organs, including the brain and spinal cord (central nervous system).
