BACE2 (E3Y9Q) Rabbit mAb #80357

β-secretase 2 (BACE2) is a type I transmembrane aspartic acid protease that catalyzes the processing of its substrates, including amyloid precursor protein (APP). Pro-BACE2 is synthesized in the endoplasmic reticulum (ER) before it is transported to the trans-Golgi network where it is cleaved by furin to become its mature form. BACE2 then migrates to the plasma membrane where it acts upon its substrates (1,2). Mature BACE2 functions as a θ-secretase, cleaving APP to produce a carboxyl-terminal fragment of 80 amino acids (C80) (3,4). Similar to its homolog BACE, BACE2 can also cleave APP at the β-site, releasing a soluble, extracellular APP-β (sAPP-β) ectodomain and generating a membrane-bound, carboxy-terminal fragment consisting of 99 amino acids (C99). Mutations within the juxtamembrane helix (JH) of APP, or the binding of this region by the neuronal chaperone protein clusterin, enables this BACE2-mediated β-cleavage. Additional processing of C99 by γ-secretase generates the amyloid β-peptide (Aβ) that forms aggregates in the brains of Alzheimer's disease (AD) patients (5).

BACE2 expression in the brain is lower, both in comparison to that of BACE and to its expression level in the periphery. However, expression of BACE2 within the brain has been seen to increase during aging and in the context of neurodegenerative disease, further supporting the role it may play in disease progression (5,6). BACE2 may also play a role in disease progression in the periphery. For instance, in the pancreas, BACE2 has been implicated in regulating β-cell function and mass in the context of type II diabetes (2,7).