AIMS β-Site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) is a biological and positional candidate gene for Alzheimer's disease (AD). Previous studies found that BACE1-null mice had impaired performance on cognition and neurodegeneration during the aging process. Additionally, a synonymous polymorphism of BACE1 (rs638405) in exon 5 has been reported to be associated with risk for AD...

BACE1 is the β-secretase enzyme that initiates production of the β-amyloid (Aβ) peptide involved in Alzheimer’s disease (AD). However, little is known about functions of BACE1. BACE1 deficient mice exhibit mild but complex neurological phenotypes suggesting therapeutic BACE1 inhibition may not be completely free of mechanism-based side effects. Recently, we have reported that BACE1 null mice ha...

Proteolytic processing of amyloid-β precursor protein (APP) by beta-site APP cleaving enzyme 1 (BACE1) is the initial step in the production of amyloid beta (Aβ), which accumulates in senile plaques in Alzheimer's disease (AD). Essential for this cleavage is the transport and sorting of both proteins through endosomal/Golgi compartments. Golgi-localized γ-ear-containing ARF-binding (GGA) protei...

Assessing BACE1 (β-site APP cleaving enzyme 1) knockout mice for general health and neurological function may be useful in predicting risks associated with prolonged pharmacological BACE1 inhibition, a treatment approach currently being developed for Alzheimer's disease. To determine whether BACE1 deletion-associated effects in mice generalize to another species, we developed a novel Bace1-/- r...

BACE1 is required for the release of beta-amyloid (Abeta) in vivo, and inhibition of BACE1 activity is targeted for reducing Abeta generation in Alzheimer's patients. To further our understanding of the safe use of BACE1 inhibitors in human patients, we aimed to study the physiological functions of BACE1 by characterizing BACE1-null mice. Here, we report the finding of spontaneous behavioral se...

We have demonstrated a prototypical hybrid classical and quantum computational workflow for the quantification of protein–ligand interactions. The combines density matrix embedding theory (DMET) procedure with variational eigensolver (VQE) approach finding molecular electronic ground states. A series ? -secretase (BACE1) inhibitors is rank-ordered using binding energy differences calculated on ...

Dipsaci Radix has been proved to represent an effective treatment strategy for Alzheimer's disease (AD), but the potential active components in have not evaluated by AD-related bioassay. In this study, water fraction of had shown highest inhibitory effect on activity tests, including inhibition acetylcholinesterase (AChE), butyrylcholinesterase (BChE), β-site amyloid precursor protein cleaving ...

The β-site APP cleaving enzyme 1 (BACE1) is a transmembrane aspartyl protease involved in Alzheimer's disease (AD) pathogenesis and in myelination. BACE1 initiates the generation of the pathogenic amyloid β-peptide, which makes BACE1 a major drug target for AD. BACE1 also cleaves and activates neuregulin 1, thereby contributing to postnatal myelination, in particular in the peripheral nervous s...

CONTEXT Activity of beta-site APP-cleaving enzyme1 (BACE1) is required for the generation of beta-amyloid peptides, the principal constituents of plaques in the brains of patients with Alzheimer's disease. Strong BACE1 expression has also been described in pancreatic tissue. OBJECTIVE The aim of the present study was to reveal the cell type-specific expression of BACE1 in the pancreas and to ...

beta-site APP cleaving enzyme 1 (BACE1) is the beta-secretase enzyme required for generating pathogenic beta-amyloid (Abeta) peptides in Alzheimer's disease (AD). BACE1 knockout mice lack Abeta and are phenotypically normal, suggesting that therapeutic inhibition of BACE1 may be free of mechanism-based side effects. However, direct evidence that BACE1 inhibition would improve cognition is lacki...