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APP alpha-secretase

Function: - may be one of several proteases cleaving the amyloid precursor protein (APP) within the region of the molecule giving rise to the A4 amyloid peptide (A-beta), thus precluding formation of A-beta - specifically it cleaves between Lys16 & Leu17 of A-beta in the exoplasmic region of APP (see membrane domain region of APP) - APP-alpha secretase cleaves both plasma membrane inserted APP & secretory vesicle-associated APP [3] - proteases with alleged APP alpha secretase activity include: a) cathepsin B b) A disintegrin & metalloproteinase domain 10 (ADAM10) c) A disintegrin & metalloproteinase domain 17 (ADAM17) - activity may be dimimished by cholesterol or cholesterol esters [2] - it has been proposed that acetylcholine receptor or muscarinic receptor stimulation may enhance APP alpha-secretase activity. [1]

Interactions

molecular events

Related

A4 amyloid peptide; beta-peptide amyloid precursor protein (APP) or A4/beta amyloid precursor protein APP secretase

Specific

A disintegrin & metalloproteinase domain 10; Kuzbanian protein homolog; mammalian disintegrin-metalloprotease; CDw156; CD156c (ADAM10, KUZ, MADM) cathepsin-B (APP alpha-secretase) CD156b, A disintegrin & metalloproteinase domain 17; TNF-alpha-converting enzyme; TNF-alpha convertase; snake venom-like protease; CD156b (ADAM17, CSVP, TACE)

General

protease; proteinase; endopeptidase

Properties

MOTIF: active site

References

  1. Cole G for Lee V. In: Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001 Mesulam M. The cholinergic lesion of Alzheimer's disease: pivotal factor or side show? Learn Mem. 2004 Jan-Feb;11(1):43-9. Review. PMID: 14747516
  2. Marx J. Science 294:508, 2001
  3. Selkoe DJ. Alzheimer's disease: genes, proteins, and therapy. Physiol Rev. 2001 Apr;81(2):741-66. Review. PMID: 11274343