Human β-site APP-Cleaving Enzyme 1,BACE1 ELISA kit

Code CSB-E09824h
Size 96T,5×96T,10×96T How to order?
Trial Size 24T ELISA kits trial application
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Product Details

Description

The ELISA Kit is designed to measure human BACE1 levels in samples, including serum, plasma, or tissue homogenates. It uses the sandwich enzyme immunoassay technique in combination with the enzyme-substrate chromogenic reaction to quantify the analyte in the sample. The color develops positively to the amount of BACE1 in samples. The color intensity is measured at 450 nm via a microplate reader.

BACE1 is an aspartic protease that catalyzes the rate-limiting, initial cleavage at the β site of amyloid precursor protein (APP) and is followed by sequential intra-membrane processing at multiple sites by γ-secretase in the production of amyloid-β (Aβ). It is widely expressed in the brain, particularly in neurons, oligodendrocytes, and astrocytes, with particular abundance in various neuronal cell types. Inhibition of BACE1 proteolytic activity has been demonstrated to reduce Aβ generation and amyloid deposition, and thus specific inhibition of BACE1 by small molecules is a current focus for Alzheimer's disease therapy. In addition to the amyloidogenic pathway, BACE1 is involved in synaptic plasticity and synaptic homeostasis.

Target Name beta-site APP-cleaving enzyme 1
Alternative Names BACE1; BACE; KIAA1149; Beta-secretase 1; Aspartyl protease 2; ASP2; Asp 2; Beta-site amyloid precursor protein cleaving enzyme 1; Beta-site APP cleaving enzyme 1; Memapsin-2; Membrane-associated aspartic protease 2
Abbreviation BACE1
Uniprot No. P56817
Species Homo sapiens (Human)
Sample Types serum, plasma, tissue homogenates
Detection Range 3.12 pg/mL-200 pg/mL
Sensitivity 0.78 pg/mL
Assay Time 1-5h
Sample Volume 50-100ul
Detection Wavelength 450 nm
Research Area Cell Biology
Assay Principle quantitative
Measurement Sandwich
Precision
Intra-assay Precision (Precision within an assay): CV%<8%
Three samples of known concentration were tested twenty times on one plate to assess.
Inter-assay Precision (Precision between assays): CV%<10%
Three samples of known concentration were tested in twenty assays to assess.
Linearity
To assess the linearity of the assay, samples were spiked with high concentrations of human BACE1 in various matrices and diluted with the Sample Diluent to produce samples with values within the dynamic range of the assay.
 SampleSerum(n=4)
1:100Average %90
Range %82-97
1:200Average %95
Range %90-100
1:400Average %92
Range %88-105
1:800Average %96
Range %85-101
Recovery
The recovery of human BACE1 spiked to levels throughout the range of the assay in various matrices was evaluated. Samples were diluted prior to assay as directed in the Sample Preparation section.
Sample TypeAverage % RecoveryRange
Serum (n=5) 9180-100
EDTA plasma (n=4)9892-105
Typical Data
These standard curves are provided for demonstration only. A standard curve should be generated for each set of samples assayed.
pg/mlOD1OD2AverageCorrected
2002.168 2.052 2.110 2.017
1001.907 1.860 1.884 1.791
501.595 1.494 1.545 1.452
251.324 1.239 1.282 1.189
12.50.906 0.874 0.890 0.797
6.250.429 0.409 0.419 0.326
3.120.277 0.269 0.273 0.180
00.096 0.090 0.093  
ELISA Data Analysis Watch ELISA data processing video & download Curve Expert if needed
Troubleshooting
and FAQs
ELISA kit FAQs
Storage Store at 2-8°C. Please refer to protocol.
Lead Time 3-5 working days

Citations

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Target Background

Function
(From Uniprot)
Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves at the N-terminus of the A-beta peptide sequence, between residues 671 and 672 of APP, leads to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated C-terminal fragment which is later released by gamma-secretase. Cleaves CHL1.
Gene References into Functions
  1. BACE1 regulates the expression of insulin receptor in the liver PMID: 29610518
  2. Results indicated that the proinflammatory cytokine TNF-alpha impairs endothelial tight junctions and promotes monocyte-endothelial cell adhesion by upregulating beta-site amyloid precursor protein enzyme 1 expression through activating PKC signaling and sequentially cleaving alpha-2, 6-sialic acid transferase 1. PMID: 28091531
  3. Study did not detect any difference in peripheral expression of BACE1 and its naturally occurring antisense in epileptic patients and healthy subjects but a significant correlation between the transcript levels of these genes. PMID: 29860633
  4. BACE1 is predominantly SUMOylated at K501 residue, which escalates its protease activity and stability and subsequently increases Abeta production. PMID: 29581300
  5. Their anti-BACE1 and antimicrobial activity. PMID: 29538306
  6. Structural arrangement of BACE1-TM trimers and a mechanism for copper ion conduction that might also apply to other proteins involved in metal ion transport. PMID: 29391167
  7. Potentials for beneficial or consequential effects resulting from pharmacologic inhibition of BACE1 are reviewed in context of ongoing clinical trials testing the effect of BACE1 candidate inhibitor drugs in Alzheimer's disease populations. PMID: 29027981
  8. Measured plasma levels of beta-secretase 1 (BACE1) long non-coding RNA(LncRNA) in Alzheimer disease (AD) patients and healthy controls; found plasma BACE1 LncRNA to be a specific biomarker for AD. PMID: 29316899
  9. Amyloid beta oligomers modulate BACE1 through an XBP-1-dependent pathway involving HRD1. PMID: 27853315
  10. Polymethoxyflavones isolated from citrus peels might be considered as promising BACE1 inhibitory agents that could lower Abeta production in Alzheimer disease. PMID: 28869548
  11. In BACE1 transgenic (Tg) mice, axonal regeneration was reduced when compared with wilde-type (WT) littermates at 3 and 10 days post crush. Study observed a decreased percentage of innervated neuromuscular junctions at 15 days post crush; and a functional recovery delay in the transgenic mice as it took 8 weeks for the compound muscle action potential amplitudes of Tg mice to begin to reach similar values comparable to WT. PMID: 28687442
  12. Our study demonstrated there may exist an association between BACE1 rs535860 polymorphism and focal seizures in Chinese Han males. PMID: 29595667
  13. This study shown that the protein expression of BACE1 is downregulated by chronic treatment with donepezil. This effect may be interpreted as evidence of disease modification. PMID: 27858713
  14. Endosome-to-TGN trafficking of BACE1 is regulated by Par3 and aPKC. This is a mechanism in pathogenesis of Alzheimer disease. PMID: 28946017
  15. Results indicate that SNX4-mediated regulation of the steady-state levels and trafficking of BACE1, as well as the subsequent increase in BACE1-mediated cleavage, may be relevant to Alzheimer's disease progression. PMID: 28109317
  16. We discuss how the underlying mechanisms can be conceived and develop scenarios how the regulation of ion conductances by BACE1 might shape electric activity in the intact and diseased brain and heart PMID: 27253079
  17. Study showed that serum deprivation enhances ADAM10/17-mediated cleavage and secretion of enzymatically active BACE1. This could be the result of alterations in the lipid composition of the membrane that lead in disruption of membrane compartmentalization in lipid rafts and non-lipid rafts. At present the significance of BACE1 shedding in the development of Alzheimer's disease is unclear. PMID: 27784219
  18. Data suggest that trimerization of BACE1 requires transmembrane sequences (TMSs) and cytoplasmic domains, with residues Ala463 and Cys466 buried within trimer interface of the sulfur-rich core of TMSs; BACE1 appears to play role in compartmentalization of intracellular copper by transferring cytosolic copper to intracellular compartments. PMID: 28637867
  19. the depletion of BIN1 increases cellular BACE1 levels through impaired endosomal trafficking and reduces BACE1 lysosomal degradation, resulting in increased Ab production. Our findings provide a mechanistic role of BIN1 in the pathogenesis of Alzheimer disease (AD), as a novel genetic regulator of BACE1 levels and Ab production PMID: 27179792
  20. in vitro BACE1-activity assays demonstrate that palmitoylation-dependent dimerization of APP promotes beta-cleavage of APP in lipid-rich detergent resistant cell membranes (DRMs), when compared to total APP. PMID: 27875558
  21. The circular RNA ciRS-7 promotes APP and BACE1 degradation in an NF-kappaB-dependent manner. PMID: 28296235
  22. rs638405 in BACE1 was not associated with the risk of Alzheimer's disease (AD), rs638405 decreased the risk of apolipoprotein-E epsilon4 (APOE4) positive AD patients, rs638405 also decreased the risk of Asian AD patients. Data of meta-analysis suggested rs638405 in BACE1 was a protective factor of AD. PMID: 26846559
  23. analysis suggests that some familial Alzheimer's disease mutations in APP are amyloidogenic and/or amyloidolytic via selection of alternative BACE1 cleavage sites PMID: 27687728
  24. In this study, we aimed to investigate the association of BACE1 rs490460 with the risk of Schizophrenia in an Iranian population. A significant association was observed between the rs490460 T allele and Schizophrenia ( p = 0.0002, odds ratio 0.69, 95% confidence interval 0.57-0.84). PMID: 28384043
  25. findings demonstrate that USP8 plays a key role in the trafficking and degradation of BACE1 by deubiquitinating lysine 501. PMID: 27302062
  26. Cassia obtusifolia extract and its major constituents are potent BACE1 inhibitors. PMID: 27321278
  27. Suggest the potential of ginsenosides (Rb1, Rb2, Rc, Re, Rg1, and Rg3) for use in the development of therapeutic or preventive agents for Alzheimer's disease, especially through inhibition of AChE, BChE and BACE1 activities, as well as scavenging of ONOO(-) and inhibition of nitrotyrosine formation. PMID: 27275774
  28. the behavior of the flap tips during simulations is different between BACE1 and BACE2. The BACE1 active site cavity is more spacious as compared to that of BACE2. The analysis of 10S loop and 113S loop showed a similar trend to that of flaps, with the BACE1 loops being more flexible and less stable than those of BACE2 PMID: 26804314
  29. Review discussing the major discoveries of the past 3 years concerning BACE1 biology and to what extent these could limit the use of BACE1 inhibitors in the clinic PMID: 26833257
  30. Study investigated baseline platelet membrane beta-secretase activity and cholesterol levels in mild cognitive impairment participants and explored whether these parameters differed in individuals who subsequently developed Alzheimer's disease PMID: 26639974
  31. Results suggest that ubiquilin-1 may mechanistically participate in Alzheimer's disease molecular pathogenesis by affecting BACE1 and thereby APP processing and Abeta accumulation PMID: 26563932
  32. Results suggest that DISC1 interacts with BACE1 and promotes lysosomal degradation of BACE1, thus reducing the generation of Abeta PMID: 26062786
  33. GG genotype and G allele of BACE1 gene rs638405 probably increase the risk of AD. [META-ANALYSIS] PMID: 26828303
  34. study reports that sAbetaPPalpha, the product of the cleavage of AbetaPP by alpha-secretase, is a potent endogenous direct inhibitor of the BACE enzyme, and that its inhibition is likely by an allosteric mechanism PMID: 26401691
  35. Results suggest deltaOR-Phe27Cys variation modulates beta- and gamma-secretase activity in late-stage Alzheimer's disease likely via post-translational mechanisms PMID: 26402014
  36. p38alpha MAPK plays a critical role in the regulation of BACE1 degradation and Abeta generation in Alzheimer Disease pathogenesis PMID: 26663083
  37. this is the first study to acquire a DNA aptamer that exhibited binding specificity to BACE1 and inhibited its activity. PMID: 26473367
  38. the Alzheimer's disease-protective 'Icelandic' mutation greatly attenuates APP-BACE-1 interactions, suggesting a mechanistic basis for protection. PMID: 26642089
  39. Studies suggest that beta-Secretases BACE1/2 plays an important role in retinal homeostasis and that BACE upregulation in response to stress is a protective measure. PMID: 26427429
  40. analysis of the differential dose-dependent effects of simvastatin on HIF-1alpha and BACE in cultured Alzheimer's disease cybrid cells PMID: 26228060
  41. BACE1 elevation in the endothelia and perivascular neurites may be involved in angiopathic Abeta deposition, while BACE1 elevation in meningeal cells might contribute Abeta to leptomeningeal amyloidosis. PMID: 25934480
  42. BACE1 overexpression-induced SET up-regulation promotes neuritic plaque formation. PMID: 24935721
  43. miR-29c was downregulated in sporadic Alzheimer disease brains, and it targeted the 3' UTR of BACE1 PMID: 25973041
  44. Use molecular docking simulations and molecular dynamics simulations to characterize binding mechanism between BACE-1 and its inhibitors. PMID: 25965961
  45. MicroRNA-29c targets BACE1 and has a neuroprotective role in vitro and in vivo. PMID: 25955795
  46. Galangin-induced down-regulation of BACE1 by epigenetic mechanisms PMID: 25779965
  47. APP is localized in pre-synaptic vesicles, where it is processed by Bace1. PMID: 25247712
  48. Results show that the inverse coupling of APP cleavage by ADAM10 and BACE1 depends on the cellular model PMID: 22940630
  49. Metformin decreases BACE1 protein expression by interfering with an mRNA-protein complex that contains the ubiquitin ligase MID1, thereby reducing BACE1 activity. PMID: 25025689
  50. greater than 50% BACE1 inhibition might be necessary to significantly lower beta-amyloid peptide PMID: 25567526

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Subcellular Location Cell membrane; Single-pass type I membrane protein. Golgi apparatus, trans-Golgi network. Endoplasmic reticulum. Endosome. Cell surface. Cytoplasmic vesicle membrane; Single-pass type I membrane protein. Membrane raft. Lysosome. Late endosome. Early endosome. Recycling endosome. Cell projection, axon. Cell projection, dendrite.
Protein Families Peptidase A1 family
Tissue Specificity Expressed at high levels in the brain and pancreas. In the brain, expression is highest in the substantia nigra, locus coruleus and medulla oblongata.
Database Links

HGNC: 933

OMIM: 604252

KEGG: hsa:23621

STRING: 9606.ENSP00000318585

UniGene: Hs.504003

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