BACE1 is the protease responsible for the production of amyloid-b peptides that accumulate in the brain of Alzheimer’s disease (AD) patients. BACE1 expression is regulated at the transcriptional, as well as post-transcriptional level. Very high BACE1 mRNA levels have been observed in pancreas, but the protein and activity were found mainly in brain. An up-regulation of the protein has been desc...

BACE1 (β-site amyloidogenic cleavage of precursor protein-cleaving enzyme 1) is a β-secretase protein that plays a central role in the production of the β-amyloid peptide in the brain and is thought to be involved in the Alzheimer's pathogenesis. In type 2 diabetes, amyloid deposition within the pancreatic islets is a pathophysiological hallmark, making crucial the study in the pancreas of BACE...

Inhibition of β-secretase BACE1 is considered one of the most promising approaches for treating Alzheimer's disease. Several structurally distinct BACE1 inhibitors have been withdrawn from development after inducing ocular toxicity in animal models, but the target mediating this toxicity has not been identified. Here we use a clickable photoaffinity probe to identify cathepsin D (CatD) as a pri...

VPS35 leaves endosomes lost in transition S luggish recycling of a protein-slicing enzyme could promote Alzheimer’s disease (AD), Wen et al. show. A , the protein that accumulates in the brains of AD patients, is formed when enzymes cut up its parental protein, known as amyloid precursor protein. One of those enzymes is -secretase or BACE1. BACE1 cycles between the Golgi apparatus and the plasm...

Amyloid β (Aβ) peptides, the primary constituents of senile plaques and a hallmark in Alzheimer's disease pathology, are generated through the sequential cleavage of amyloid precursor protein (APP) by β-site APP cleaving enzyme 1 (BACE1) and γ-secretase. The early endosome is thought to represent a major compartment for APP processing; however, the mechanisms of how BACE1 encounters APP are lar...

Beta-site APP cleaving enzyme 1 (BACE1) is a transmembrane aspartyl protease with a lumenal active site that sheds the ectodomains of membrane proteins through juxtamembrane proteolysis. BACE1 has been studied principally for its role in Alzheimer's disease as the beta-secretase responsible for generating the amyloid-beta protein. Emerging evidence from mouse models has identified the importanc...

The copper chaperone for superoxide dismutase (CCS) binds to both the β-site AβPP cleaving enzyme (BACE1) and to the neuronal adaptor protein X11α. BACE1 initiates AβPP processing to produce the amyloid-β (Aβ) peptide deposited in the brains of Alzheimer's disease patients. X11α also interacts directly with AβPP to inhibit Aβ production. However, whether CCS affects AβPP processing and Aβ produ...

Alzheimer's disease (AD) is widely considered to be caused by amyloid-β peptide (Aβ) accumulation in the brain. Aβ is excised from amyloid-β precursor protein through sequential cleavage by β-secretase 1 (BACE1) and γ-secretase. Thus, BACE1 inhibition could prevent Aβ accumulation. Here, we identified myo-inositol hexakisphosphate (IP6) as a BACE1 inhibitory molecule in rice grain extract and d...

Heparin sustains the brain myloid plaque formation can be inhibited by an unlikely culprit, according to work by Scholefield et al. on page 97. The group finds that heparan sulfate (HS)—normally a part of the cell surface and extracellular matrix—functions in cells to slow the production of the plaque components of Alzheimer's disease. Amyloid plaques are aggregates of the amyloid ␤-peptide (A ...

BACE1 is the protease responsible for the production of amyloid-b peptides that accumulate in the brain of Alzheimer’s disease (AD) patients. BACE1 expression is regulated at the transcriptional, as well as post-transcriptional level. Very high BACE1 mRNA levels have been observed in pancreas, but the protein and activity were found mainly in brain. An up-regulation of the protein has been desc...