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|CSC-SC001291||Panoply™ Human BACE1 Over-expressing Stable Cell Line||Inquiry|
|AD01681Z||Human BACE1 adenoviral particles||Inquiry|
|LV06007L||human BACE1 (NM_001207048) lentivirus particles||Inquiry|
|LV06008L||human BACE1 (NM_138972) lentivirus particles||Inquiry|
|LV06009L||human BACE1 (NM_001207049) lentivirus particles||Inquiry|
|LV06010L||human BACE1 (NM_138971) lentivirus particles||Inquiry|
|LV06011L||human BACE1 (NM_138973) lentivirus particles||Inquiry|
|LV06012L||human BACE1 (NM_012104) lentivirus particles||Inquiry|
|CDCB157344||Mouse BACE1 ORF clone (NM_011792.4)||Inquiry|
|CDCB179087||Danio rerio BACE1 ORF Clone (NM_205704)||Inquiry|
|CDCB191655||Rabbit BACE1 ORF clone (XM_002708373.2)||Inquiry|
|CDCG001458||Mouse BACE1 ORF clone(NM_011792.5)||Inquiry|
|CDCR032928||Mouse Bace1 ORF clone (NM_001145947.1)||Inquiry|
|CDCR032934||Human BACE1 ORF clone (NM_001207049.1)||Inquiry|
|CDCR032936||Human BACE1 ORF clone (NM_001207048.1)||Inquiry|
|CDCR378364||Rat Bace1 ORF Clone(NM_019204.1)||Inquiry|
|CDCS409707||Human BACE1 ORF Clone (BC065492)||Inquiry|
|CDFR011501||Rat Bace1 cDNA Clone(NM_019204.1)||Inquiry|
|MiUTR1R-00504||BACE1 miRNA 3'UTR clone||Inquiry|
|MiUTR3H-06677||BACE1 miRNA 3'UTR clone||Inquiry|
|SHG066877||shRNA set against Rat Bace1(NM_019204.1)||Inquiry|
|SHH244562||shRNA set against Human BACE1 (NM_138973.3)||Inquiry|
|SHH244568||shRNA set against Mouse BACE1 (NM_011792.5)||Inquiry|
|SHH244570||shRNA set against Rat BACE1 (NM_019204.1)||Inquiry|
|SHW017612||shRNA set against Danio rerio BACE1 (NM_205704)||Inquiry|
The production of 40 or 42 amino acids long amyloid-β peptide accumulated in the brain is the central pathological feature of Alzheimer's disease and largely consists of amyloid-β peptides. Amyloid-β is formed through sequential proteolytic processing of the amyloid precursor protein (APP), catalyzed by the β- and γ-secretases. The aspartyl protease β-site APP cleaving enzyme 1 (BACE1) cleaves APP predominantly at a unique site, whereas the c-secretase complex cleaves the resulting carboxy-terminal fragment at several sites, with preference for positions 40 and 42, leading to formation of amyloid β1-40 (Aβ1-40) and Aβ1-42 peptides.
Extracellular cleavage of APP by BACE1 produces soluble extracellular fragments 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 γ-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 α-secretase instead of BACE1 prevents the final production of amyloid-β. Unlike APP and the presenilin proteins important in γ-secretase, no known mutations in the gene encoding BACE1 lead to early-onset, familial Alzheimer's disease, which is a rare form of the disorder. Nevertheless, it has been shown that this level of enzyme is elevated in the more common late-onset sporadic Alzheimer's disease. The physiological purpose of BACE cleavage of APP and other transmembrane proteins is unclear. BACE2 is a close homolog of BACE1 and there is no reported APP cleavage in vivo. However, single residue mutations in APP reduce the ability of BACE1 to cleave it to produce amyloid-beta and reduce the risk of Alzheimers and other cognitive declines. Thorlakur et al. has shown that a coding mutation (A673T) in the APP gene that protects against Alzheimer’s disease and cognitive decline in the elderly without Alzheimer’s disease. This substitution is adjacent to the aspartyl protease β-site in APP, and results in an approximately 40% reduction in the formation of amyloidogenic peptides in vitro. The A673T substitution is located at position 2 in the amyloid-β peptide.
Fig 1. Processing of the amyloid precursor protein.
Wanxia et al. has identificated reticulon family members as binding partners of BACE1. RTN3 and RTN4B are members of the reticulon family, all of which contain a highly conserved reticulon homology domain (RHD) of about 188 amino acids with two putative transmembrane regions separated by a 66-residue loop. They found that two membrane-associated proteins, RTN3 and RTN4B, are both present in BACE1 immunocomplexes. The reticulon family of cellular proteins interacts with BACE1 and decreases both BACE1 cleavage of APP and Aβ production. RTN3 is the principal BACE1-interacting protein in human brain. It seems conceivable that small changes in reticulon expression in human brain might potentially affect long-term Aβ production and that, in turn, this could either accelerate or decelerate the deposition of amyloid in brain. Overexpression of RTN3 can inhibit Aβ production, owing to the sequestering of BACE1 away from its cellular APP substrate. Reticulon proteins share a highly conserved membrane-associated RHD, but their N-terminal regions are divergent. All tested reticulon proteins bind to BACE1 and inhibit its activity, suggesting that reticulon proteins have shared functions in addition to the specific roles mediated by their distinct N-terminal domains. The physiological meaning of the binding of reticulon proteins to BACE1 remains to be discovered. It is also unclear whether or not BACE1 binds to reticulon proteins directly. It is possible that the binding of BACE1 to reticulon proteins is in an ‘on-and-off’ state in cells because the binding of endogenous proteins is clearly weak. Increasing the expression of either RTN3 or BACE1 increased this binding and the increase in binding clearly blocked the interaction of BACE1 with its cellular APP substrate and reduced the catalytic action of BACE1.
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