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BACE/Beta-secretase-enzyme

What is BACE ?

Beta-secretase (BACE) is an aspartic-acid protease important in the formation of myelin sheaths in peripheral nerve cells. The transmembrane protein contains two active site aspartate residues in its extracellular protein domain and may function as a dimer. BACE1, as also β-site amyloid precursor protein cleaving enzyme 1, is an aspartic protease, which is a family of protease enzymes that use an aspartate residue for the catalysis of their substrates. BACE2 is a homologue of BACE1 that is mapped to the DS critical region. BACE2, however, does not appear to be the major beta-secretase and cannot compensate for loss of BACE function. BACE may be an important new therapeutic target for treatment of Alzheimer's disease.

BACE in Alzheimer's disease

Alzheimer's disease (AD) is caused by aggregates of the amyloid-β, which is generated by cleavage of the amyloid precursor protein (APP) by beta-secretase (BACE-1) followed by gamma-secretase. The beta amyloid (Aβ) is generated by two enzymes which cut APP at two different positions: β-secretase cuts APP at a position outside the cell and γ-secretase which cuts APP at a position inside the cell membrane.

Extracellular cleavage of APP by BACE1 creates a soluble extracellular fragment and a cell membrane-bound fragment referred to as C99. Cleavage of C99 within its transmembrane domain by γ-secretase releases the intracellular domain of APP and produces amyloid-β. Since gamma-secretase cleaves APP closer to the cell membrane than BACE1 does, it removes a fragment of the amyloid-β peptide. Initial cleavage of APP by gamma-secretase rather than BACE1 prevents eventual generation of amyloid-β. BACE1 can be transported from endosomes to lysosomes by ubiquitination with help from the sorting proteins, ADP ribosylation factor 6 (ARF6) and GGA3, another member of the GGA family.

Beta-secretase (BACE) is an aspartic-acid protease which an important new therapeutic target for treatment of Alzheimer's disease. BACE1 is a vertebrate-specific enzyme, which, together with presenilin-dependent γ-secretase, cleaves APP to generate the neurotoxic amyloid-β peptide (Aβ).

BACE/Beta-secretase Products List

BACE1/Beta-secretase 1 BACE2/Beta secretase 2  
Please note: All products are "FOR RESEARCH USE ONLY AND ARE NOT INTENDED FOR DIAGNOSTIC OR THERAPEUTIC USE"