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

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

  • 中文名称：
    人β位淀粉样前体蛋白裂解酶1（BACE1）酶联免疫试剂盒
  • 货号：
    CSB-E09824h
  • 规格：
    96T/48T
  • 价格：
    ￥3600/￥2500
  • 其他：

产品详情

  • 产品描述：

    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.

  • 别名：
    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
  • 缩写：
    BACE1
  • Uniprot No.：
  • 种属：
    Homo sapiens (Human)
  • 样本类型：
    serum, plasma, tissue homogenates
  • 检测范围：
    3.12 pg/mL-200 pg/mL
  • 灵敏度：
    0.78 pg/mL
  • 反应时间：
    1-5h
  • 样本体积：
    50-100ul
  • 检测波长：
    450 nm
  • 研究领域：
    Cell Biology
  • 测定原理：
    quantitative
  • 测定方法：
    Sandwich
  • 精密度：
    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.    
                 
  • 线性度：
    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.
    　 Sample Serum(n=4)  
    1:100 Average % 90  
    Range % 82-97  
    1:200 Average % 95  
    Range % 90-100  
    1:400 Average % 92  
    Range % 88-105  
    1:800 Average % 96  
    Range % 85-101  
  • 回收率：
    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 Type Average % Recovery Range  
    Serum (n=5) 91 80-100  
    EDTA plasma (n=4) 98 92-105  
                 
                 
  • 标准曲线：
    These standard curves are provided for demonstration only. A standard curve should be generated for each set of samples assayed.
    pg/ml OD1 OD2 Average Corrected  
    200 2.168 2.052 2.110 2.017  
    100 1.907 1.860 1.884 1.791  
    50 1.595 1.494 1.545 1.452  
    25 1.324 1.239 1.282 1.189  
    12.5 0.906 0.874 0.890 0.797  
    6.25 0.429 0.409 0.419 0.326  
    3.12 0.277 0.269 0.273 0.180  
    0 0.096 0.090 0.093 　  
  • 数据处理：
  • 货期：
    3-5 working days

产品评价

靶点详情

  • 功能：
    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.
  • 基因功能参考文献：
    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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  • 亚细胞定位：
    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.
  • 蛋白家族：
    Peptidase A1 family
  • 组织特异性：
    Expressed at high levels in the brain and pancreas. In the brain, expression is highest in the substantia nigra, locus coruleus and medulla oblongata.
  • 数据库链接：

    HGNC: 933

    OMIM: 604252

    KEGG: hsa:23621

    STRING: 9606.ENSP00000318585

    UniGene: Hs.504003