Beta Secretase beta-site APP cleaving enzyme 2B

Beta-secretase beta-site APP cleaving enzyme 1/2 (BACE1/2), are membrane-bound aspartyl proteases are rate limiting enzymes in the production of amyloid beta peptides, the primary component of senile plaque pathology in Alzheimer’s disease (AD).  The beta amyloid peptides are derived from APP by sequential cleavages of beta and gamma-secretases.  The beta-site APP cleaving enzyme (BACE) are the major beta seretases in vivo.  There are 2 types of BACE, BACE 1 and BACE 2. BACE 2 is located on chromosome 21 and it is speculated that BACE 2 may play a role in AD and Down syndrome (DS) also called Trisomy 21. BACE 2 cleaves APP at a novel theta site down stream of the alpha site (1).  Over-expression of BACE 2 reduced Abeta production in primary neurons derived from Swedish mutant APP transgenic mice (1).  The regulatory regions of the BACE gene contain several functional domains but lack the canonical TATA and CAAT boxes.  BACE1 gene contains several repetitive elements compared to non in BACE 2 gene.  BACE 2 is under several transcriptional regulatory pathways which partially suppress the expression of BACE 2 in normal neuronal cells and exhibit highly regulated tissue-specific gene expression (2).  BACE 2 is highly expressed in breast cancer and may be involved in normal and abnormal process of muscle biology (3). 

BACE 2 is secreted as a prozymogen requiring the cleavage of its pro sequence during the maturation process.  BACE 2 also interacts with neuronal receptor for APP called SorLA and it affect the intracellular transport and processing (3).  APP Crystal structure of BACE 2 reveals the general fold of A1 aspartic proteases.  The crystal structure of BACE 2 also reveals differences in the S3, S2, S1 active site substrate pocket.  These differences will facilitate designing BACE 2 and BACE 1 selective inhibitors.  At least 3 subtypes of BACE 2 enzymes are cloned (BACE2A, 2B and 2C), the relative expression of these three subtypes is not known.  FabGennix International Inc., have produced antibodies to BACE2A/C and BACE2B variants.    The BACE2B-selective antibodies were generated against unique antigenic sequences form near C-terminal end (aa 379-396) of the BACE2 A 2 gene.  The antibodies to BACE2A/C are affinity purified over immobilized antigen based chromatography, and the purified immunoglobulins are stabilized in antibody stabilization buffer.  FabGennix Int. Inc., will also provide limited quantities of antigenic blocking peptides for BACE2-201AP.  Antibodies to BACE 2A/C (BACE-201AP) will label the 2A and 2C variants.  BACE2B  and several other Alzheimer targets antibodies are also available from FabGennix International Inc.  For a complete listing visit www.FabGennix.com.  FabGennix Inc. will also conjugate antibodies with secondary enzymes (alk-Pase or HRP) or fluorescent probes upon request at a nominal cost.     

For research use only, not for diagnostic or therapeutic use.