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- Alpha_secretase abstract "Alpha secretases are a family of proteolytic enzymes that cleave amyloid precursor protein (APP) in its transmembrane region. Specifically, alpha secretases cleave within the fragment that gives rise to the Alzheimer's disease-associated peptide amyloid beta when APP is instead processed by beta secretase and gamma secretase. The alpha-secretase pathway is the predominant APP processing pathway. Thus, alpha-secretase cleavage precludes amyloid beta formation and is considered to be part of the non-amyloidogenic pathway in APP processing. 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. Upon cleavage by alpha secretases, APP releases its extracellular domain - a fragment known as APPsα - into the extracellular environment in a process known as ectodomain shedding.ADAM10 consists of two protein domains, a disintegrin domain and a prodomain; however, only the prodomain is required for APP processing. Other ADAM proteins, ADAM17 (also called TACE, tumor necrosis factor-α converting enzyme), ADAM9, and ADAM19 have also been identified as alpha secretases; extracellular expression of mutant ADAM9 (also known as MDC9 or meltrin gamma) lacking the membrane anchor domain has been suggested as one of many possible means of Alzheimer's prevention and treatment exploiting the alpha secretase pathway. Two distinct modalities of alpha-secretase activity have been observed in cells; constitutive activity occurs mainly at the cell surface and is independent of regulatory mechanisms inside the cell, while regulated activity occurs mainly in the golgi and is dependent on the activity of protein kinase C. Alpha-secretase activity in the golgi is thought to compete directly with the beta-secretase pathway for APP substrates during membrane protein maturation. Cell-surface cleavage by alpha secretase is very rapid after APP reaches the cell surface.The activity of alpha secretases has been implicated in the regulation of learning and memory formation. Release of the APPsα ectodomain has neurotrophic effects that counteract apoptotic signaling and promote synapse formation, processes that are upregulated when ADAM10 is overexpressed. Alpha secretase activity has also been observed to be upregulated in response to the signaling peptide PACAP.Related alpha-secretases, including ADAM10, have also been implicated in similar maturation events for other transmembrane proteins such as MHC class I proteins. Recent evidence suggests that some such proteins are first processed to ectodomains by alpha secretases and subsequently cleaved by another Alzheimer's-associated protease complex, gamma secretase in its presenilin-complexed form. The Notch pathway bears many similarities to APP processing and is also regulated in part by ADAM10.".
- Alpha_secretase thumbnail APP_cleavage.png?width=300.
- Alpha_secretase wikiPageID "9784471".
- Alpha_secretase wikiPageLength "9006".
- Alpha_secretase wikiPageOutDegree "38".
- Alpha_secretase wikiPageRevisionID "702103452".
- Alpha_secretase wikiPageWikiLink ADAM10.
- Alpha_secretase wikiPageWikiLink ADAM17.
- Alpha_secretase wikiPageWikiLink ADAM19.
- Alpha_secretase wikiPageWikiLink ADAM9.
- Alpha_secretase wikiPageWikiLink ADAM_(protein).
- Alpha_secretase wikiPageWikiLink Alzheimers_disease.
- Alpha_secretase wikiPageWikiLink Amyloid_beta.
- Alpha_secretase wikiPageWikiLink Amyloid_precursor_protein.
- Alpha_secretase wikiPageWikiLink Apoptosis.
- Alpha_secretase wikiPageWikiLink Beta-secretase_1.
- Alpha_secretase wikiPageWikiLink Category:Alzheimers_disease.
- Alpha_secretase wikiPageWikiLink Category:EC_3.4.24.
- Alpha_secretase wikiPageWikiLink Category:Membrane_proteins.
- Alpha_secretase wikiPageWikiLink Cell_(biology).
- Alpha_secretase wikiPageWikiLink Cell_membrane.
- Alpha_secretase wikiPageWikiLink Cell_surface_receptor.
- Alpha_secretase wikiPageWikiLink Disintegrin.
- Alpha_secretase wikiPageWikiLink Enzyme.
- Alpha_secretase wikiPageWikiLink Gamma_secretase.
- Alpha_secretase wikiPageWikiLink Golgi_apparatus.
- Alpha_secretase wikiPageWikiLink MHC_class_I.
- Alpha_secretase wikiPageWikiLink Memory.
- Alpha_secretase wikiPageWikiLink Metalloproteinase.
- Alpha_secretase wikiPageWikiLink Multiprotein_complex.
- Alpha_secretase wikiPageWikiLink Neurotrophin.
- Alpha_secretase wikiPageWikiLink Notch_signaling_pathway.
- Alpha_secretase wikiPageWikiLink Peptide.
- Alpha_secretase wikiPageWikiLink Pituitary_adenylate_cyclase-activating_peptide.
- Alpha_secretase wikiPageWikiLink Presenilin.
- Alpha_secretase wikiPageWikiLink Protein_domain.
- Alpha_secretase wikiPageWikiLink Protein_kinase_C.
- Alpha_secretase wikiPageWikiLink Proteolysis.
- Alpha_secretase wikiPageWikiLink Substrate_(chemistry).
- Alpha_secretase wikiPageWikiLink Synapse.
- Alpha_secretase wikiPageWikiLink Transmembrane_protein.
- Alpha_secretase wikiPageWikiLink File:APP_cleavage.png.
- Alpha_secretase wikiPageWikiLinkText "Alpha secretase".
- Alpha_secretase wikiPageWikiLinkText "alpha secretase".
- Alpha_secretase wikiPageWikiLinkText "α-".
- Alpha_secretase wikiPageWikiLinkText "α-secretase".
- Alpha_secretase wikiPageWikiLinkText "α‐secretase".
- Alpha_secretase wikiPageUsesTemplate Template:Enzymes.
- Alpha_secretase wikiPageUsesTemplate Template:Metalloendopeptidases.
- Alpha_secretase wikiPageUsesTemplate Template:Portal_bar.
- Alpha_secretase wikiPageUsesTemplate Template:Proteases.
- Alpha_secretase wikiPageUsesTemplate Template:Reflist.
- Alpha_secretase subject Category:Alzheimers_disease.
- Alpha_secretase subject Category:EC_3.4.24.
- Alpha_secretase subject Category:Membrane_proteins.
- Alpha_secretase hypernym Family.
- Alpha_secretase type Disorder.
- Alpha_secretase comment "Alpha secretases are a family of proteolytic enzymes that cleave amyloid precursor protein (APP) in its transmembrane region. Specifically, alpha secretases cleave within the fragment that gives rise to the Alzheimer's disease-associated peptide amyloid beta when APP is instead processed by beta secretase and gamma secretase. The alpha-secretase pathway is the predominant APP processing pathway.".
- Alpha_secretase label "Alpha secretase".
- Alpha_secretase sameAs Q908080.
- Alpha_secretase sameAs Alpha-Sekretasen.
- Alpha_secretase sameAs Alfasekretaasi.
- Alpha_secretase sameAs m.02ps340.
- Alpha_secretase sameAs Q908080.
- Alpha_secretase wasDerivedFrom Alpha_secretase?oldid=702103452.
- Alpha_secretase depiction APP_cleavage.png.
- Alpha_secretase isPrimaryTopicOf Alpha_secretase.