A portrait of Alzheimer secretases--new features and familiar faces.
The amyloid beta-peptide (Abeta) is a principal component of the cerebral plaques found in the brains of patients with Alzeheimer's disease (AD). This insoluble 40- to 42-amino acid peptide is formed by the cleavage of the Abeta precursor protein (APP). The three proteases that cleave APP, alpha-, beta-, and gamma-secretases, have been implicated in the etiology of AD. beta-Secretase is a membrane-anchored protein with clear homology to soluble aspartyl proteases, and alpha-secretase displays characteristics of certain membrane-tethered metalloproteases. gamma-Secretase is apparently an oligomeric complex that includes the presenilins, which may be the catalytic component of this protease. Identification of the alpha-, beta-, and gamma-secretases provides potential targets for designing new drugs to treat AD.
Esler
W P
WP
Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Wolfe
M S
MS
D051722:ADAM Proteins; D000072198:ADAM17 Protein; D000544:Alzheimer Disease / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D053829:Amyloid Precursor Protein Secretases; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D001921:Brain / Q000201:enzymology; D020134:Catalytic Domain; D019281:Dimerization; D010450:Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000737:chemistry / Q000378:metabolism; D053764:Presenilin-1; D053766:Presenilin-2; D051880:Receptors, Notch; D015398:Signal Transduction
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2; D051880:Receptors, Notch; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509284:BACE2 protein, human; C509280:BACE1 protein, human; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000072198:ADAM17 Protein