By Takaomi Comings Saido
Beta-secretase M. Citron Alpha-secretases S. Ishiura ADAM 10/alpha secretase and presenilins/gamma secretase in APP processing and notch signaling D. Hartmann Gamma-secretase and presenilin M. Wolfe Biochemistry of gamma-secretase (tentative identify) S. Sinha Presenilin and intracellular protein delivery Degradation of Abeta by way of neprilysin T.C. Saido Degradation of Abeta through endothelin-converting enzyme C. Eckman Degradation of Abeta through insulin-degrading enzyme Lipid raft and Abeta metabolism T. Golde Lipid raft and Abeta accumulation M. Morishima-Kawashima and Y. Ihara Transport-dependent clearance of Abeta B. Zlokovic Abeta vaccination C. Lemere
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Extra resources for A-Beta Metabolism and Alzheimer's Disease (Neuroscience Intelligence Unit 7)
Kitazume S, Tachida Y, Oka R et al. Alzheimer’s β-secretase, β-site amyloid precursor protein cleaving enzyme, is responsible for cleavage secretion of a Golgi-resident sialyltransferase. Proc Natl Acad Sci 2001; 98:13554-13559. 43. Lichtenthaler S, Seed B. The aspartyl protease BACE regulates the shedding of p-selectin glycoprotein ligand-1. Neurobiol Aging 2002; 23:S175-S176. 44. Holsinger RMD, McLean CA, Masters CL et al. BACE and β-secretase product CTFβ are increased in sporadic Alzheimer’s disease brain.
1. ADAM family +: proteolytic activity confirmed; -: not confirmed. 15 When we transfected APP695-LAA in which HHQK of Aβ13-16 is replaced with LHHAA to confer greater resistance to α-secretory cleavage, phorbol ester failed to activate α-cleavage, indicating that regulated cleavage is conducted by ADAM9. We also found that a general metalloprotease inhibitor SI-27 inhibited the phorbol ester-induced increase in sAPPα secretion together with concomitant increase in sAPPβ secretion. 14 Purified recombinant mADAM9 could cleave APP in vitro at α-cleavage site.
38. Saido TC, Iwatsubo T, Mann DMA et al. Dominant and differential deposition of distinct β-amyloid peptide species, AβN3(pE), in senile plaques. Neuron 1995; 14:457-466. 39. Russo C, Schettini G Saido TC et al. Preferential deposition of truncated amyloid-β peptides in brain of presenilin 1 gene mutation carriers. Nature 2000;, 405: 531-532. 40. Jarrett JT, Lansbury Jr PT. Seeding “one-dimensional crystallization” of amyloid: a pathogenic mechanism in Alzheimer’s disease and scrapie? Cell 1993; 73(6):1055-8.