P-secretase BACE

Alzheimer disease is characterized by the formation of amyloid plaques composed by accumulated neurotoxic p-amyloid peptides. These peptides are generated from amyloid precursor protein by proteolytic processing implicating the protease p-secretase BACE-1. The proteolytic degradation of the amyloid precursor protein can be modulated by inhibition of the BACE-1. Boons et synthesized well-defined HS oligosaccharides and found that one tetrasaccharide was able to inhibit it well. Tyler et al synthesized a library of 16 HS hexa- to dodecasaccharides. Screening of... 

BACE-1 (p-secretase) is one of the enzymes involved in breaking down APP to produce Ap (amyloid p-peptide, Ap40>42), the protein that eventually oligomerizes to form Ap plaques, the hallmark of Alzheimer s disease (AD). Thus an agent that... 

Vassar, R., Bennett, B. D., Babu-Khan, S. et al. P-secretase cleavage of Alzheimer s amyloid precusor protein by the transmembrane aspartic protease BACE. Science 286 735-741, 1999. 

Bennett, B.D., Denis, P., Haniu, M., Teplow, D.B., Kahn, S., Louis, J.C., Citron, M. and Vassar, R. 2000b. A furin-like convertase mediates propeptide cleavage of BACE, the Alzheimer s P-secretase. J. Biol. Chem. 275 37712-37717... 

Using a similar strategy, the activity of BACE (p-site of APP-cleaving enzyme), which is an aspartic protease that cleaves the amyloid precursor protein (APP), the P-secretase site was detected at nanogram scale. The activated fluorescence signal was detected conveniently using an optical imaging instrument (Fig. 4). 

Vassar R, Bennett BD, Babu-Khan S, Kahn S, Mendiaz EA, Denis P, Teplow DB, Ross S, Amarante P, Loeloff R, Luo Y, Fisher S, Fuller J, Edenson S, File J, Jarosinski MA, Biere AL, Curran E, Burgess T, Louis JC, Collins F, Treanor J, Rogers G Citron M. (1999) Beta-secretase cleavage of Alzheimer s amyloid precursor protein by the transmembrane aspartic protease BACE. Science 286 735-741. 

Gruninger-Leitch F, Schlatter D, Kung E, Nelbock P, Dobeli H. 2002. Substrate and inhibitor profile of BACE (beta-secretase) and comparison with other mammalian aspartic proteases. J. Biol. Chem. 277 4687-93... 

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