Beta-site amyloid precursor protein cleaving

Willem M, Dewachter I, Smyth N, Van Dooren T, Borghgraef P, Haass C, Van Leuven F (2004) beta-site amyloid precursor protein cleaving enzyme 1 increases amyloid deposition in brain parenchyma but reduces cerebrovascular amyloid angiopathy in aging BACE x APP[V717I] double-transgenic mice. Am J Pathol 165 1621-1631. 

Huse JT, Pijak DS, Leslie GJ, Lee VM, Dorns RW. 2000. Maturation and endoso-mal targeting of beta-site amyloid precursor protein-cleaving enzyme. The Alzheimer s disease beta-secretase. J. Biol. Chem. 275 33729-37... 

Puglielli, L., Ellis, B. C., Saunders, A. J., and Kovacs, D. M. Ceramide stabilizes beta-site amyloid precursor protein-cleaving enzyme 1 and promotes amyloid beta-peptide biogenesis. J Biol Chem 278 (2003) 19777-19783. 

The pictorial representation on the tide page of this book symbolizes how the different lead generation methods need to work together to spin the LG wheel to deliver high quality lead series. The molecule depicted is an early lead against the beta-site amyloid precursor protein cleaving enzyme 1 (BACEl) [44]. 

Beta-site amyloid precursor protein [APP]-cleaving enzyme Brain-derived neurotrophic factor Cornu ammonis... 

To elucidate potential mechanisms by which stress exacerbated Ap-induced impairment of cognitive abilities and synaptic plasticity, the levels of signaling molecules important for these processes have been evaluated. Results show that combination of chronic stress and Ap reduced the basal levels of P-CaMKII and P-CREB in area CAl of the hippocampus, more markedly than either condition alone [86, 87, 261]. Chronic nicotine treatment, on the other hand, completely prevents the effect of the combination on P-CaMKII and P-CREB levels [87, 261]. The combination of chronic stress and Ap also elevates the basal levels of calcineurin in area CAl of the hippocampus [86, 87, 260]. This elevation is also prevented by chronic nicotine treatment [87, 260]. Combination of chronic stress and Ap suppresses the expected E-LTP-induced increase in CaMKII phosphorylation and L-LTP-induced increase in CREB phosphorylation and CaMKIV protein expression in area CAl [86, 87]. These E-LTP- and L-LTP-induced expression of signaling molecules are restored by chronic nicotine treatment [87]. Furthermore, chronic stress has been shown to intensify the increase in protein levels of Ap and beta-site amyloid precursor protein [APP]-cleaving enzyme [BACE] in area CAl of Ap-treated rat. This elevation is normalized by chronic nicotine treatment [262]. Additionally, the levels of the a7, p4, and p2 subunits of nAChRs are significantly decreased in Ap rats, but these are also normalized in Ap rats chronically treated with nicotine. 

Spoelgen, R., von Arnim, C.A., Thomas, A.V., et al. (2006) Interaction of the cytosolic domains of sorLA/LRll with the amyloid precursor protein (APP) and beta-secretase beta-site APP-cleaving enzyme. J. Neurosci., 26, 418-428. 

LinX, Koelsch G, Wu S,Downs D,Dashti A, Tang J. 2000. Human aspartic protease memapsin 2 cleaves the beta-secretase site of beta-amyloid precursor protein. Proc. Natl. Acad. Sci. USA 97 1456-60... 

Hussain I, Powell DJ, Howlett DR, Chapman GA, Gilmour L, et al. 2000. ASP1 (BACE2) cleaves the amyloid precursor protein at the beta-secretase site. Mol. Cell. Neurosci. 16 609-19... 

Farzan M, Schnitzler CE, Vasilieva N, Leung D, Choe H (2000) BACE2, a beta-secretase homolog, cleaves at the beta site and within the amyloid-beta region of the amyloid-beta precursor protein. Proc Natl Acad Sci USA 97 9712-9717... 

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