We would be very pleased if you would consider our manuscript for publication in Biochemical and Biophysical Research Communications. Below is a brief summary of the background and purpose of our study. In this report, we demonstrated that mPGES-2 can be cleaved by BACE-1, which leads to neuroinflammation in the brain. In addition to APP, novel substrates of BACE-1 have been identified. Further...

is higher in neurons of the brain. (2) BACE is localized within acidic intracellular compartments. (3) Overex-pression of BACE in cells increases ␤-secretase cleav-age products; these products start only at known ␤-secre-tase cleavage sites. (4) Antisense inhibition of BACE in cells decreases ␤-secretase cleavage. (5) Purified forms of BACE cleave APP substrates in vitro with correct ␤-secretas...

β-secretase (BACE-1), an enzyme critical in the process of amyloid-β (Aβ) peptides deposition in human brain, is closely associated with the onset and progression of Alzheimer's disease (AD). A strong need exists, therefore, to identify molecular imaging probes homing at BACE-1 for use with positron emission tomography (PET) that is recognized as an effective tool for detecting AD. Through this...

Amyloid precursor protein (APP) and β-site APP cleaving enzyme (BACE-1) play important roles in the pathogenesis of Alzheimer's disease (AD). In this study, using bioinformatics analysis, we demonstrate that miR-384 is a microRNA (miRNA or miR) predicted to potentially target the 3' untranslated regions (3'-UTRs) of both APP and BACE-1. SH-SY5Y cells were transfected with miR-384 mimic oligonuc...

The prion protein (PrP) and the beta-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE-1) are both copper binding proteins, but are associated with two separate neurodegenerative diseases. The role of BACE-1 in the formation of beta-amyloid has made it a major target in attempts to reduce the formation of beta-amyloid in Alzheimer's diseases. However, the suggestion that PrP, normall...

BACKGROUND Several lines of investigation support the notion that endocytosis is crucial for Alzheimer's disease (AD) pathogenesis. Substantial evidence have already been reported regarding the mechanisms underlying amyloid precursor protein (APP) traffic, but the regulation of beta-site APP-Cleaving Enzyme 1 (BACE-1) distribution among endosomes, TGN and plasma membrane remains unclear. Dynami...

The critical role of BACE-1 in the formation of neurotoxic ß-amyloid peptides in the brain makes it an attractive target for an efficacious treatment of Alzheimer's disease. However, the development of clinically useful BACE-1 inhibitors has proven to be extremely challenging. In this study we examine the binding mode of a novel potent inhibitor (compound 1, with IC50 80 nM) designed by synergi...

Three series of 3-(2-aminoheterocycle)-4-benzyloxyphenylbenzamide derivatives, 2-aminooxazoles, 2-aminothiazoles, and 2-amino-6H-1,3,4-thiadizines were designed, synthesized and evaluated as β-secretase (BACE-1) inhibitors. Preliminary structure-activity relationships revealed that the existence of a 2-amino-6H-1,3,4-thiadizine moiety and α-naphthyl group were favorable for BACE-1 inhibition. A...

-Secretase (BACE, Asp-2) is a transmembrane aspartic proteinase responsible for cleaving the amyloid precursor protein (APP) to generate the soluble ectodomain sAPP and its C-terminal fragment CTF . CTF is subsequently cleaved by -secretase to produce the neurotoxic synaptotoxic amyloidpeptide (A ) that accumulates in Alzheimer’s disease. Indirect evidence has suggested that amyloidogenic APP p...