Bace1

Summary

Gene Symbol: Bace1
Description: beta-secretase 1
Alias: Bace, beta-secretase 1, ASP2, asp 2, aspartyl protease 2, beta-site APP cleaving enzyme 1, beta-site amyloid precursor protein cleaving enzyme 1, memapsin-2, membrane-associated aspartic protease 2
Species: rat
Products:     Bace1

Top Publications

  1. Zhang Y, Xiong M, Yan R, Sun F. Mutant ubiquitin-mediated beta-secretase stability via activation of caspase-3 is related to beta-amyloid accumulation in ischemic striatum in rats. J Cereb Blood Flow Metab. 2010;30:566-75 pubmed publisher
    ..have demonstrated that ischemic stroke increases beta-amyloid (Abeta) production by increasing beta-secretase (BACE1) through activation of caspase-3, and stimulates generation of mutant ubiquitin (UBB(+1)) in rat brains...
  2. Vassar R, Bennett B, Babu Khan S, Kahn S, Mendiaz E, Denis P, et al. Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE. Science. 1999;286:735-41 pubmed
    ..Overexpression of this protease, termed BACE (for beta-site APP-cleaving enzyme) increased the amount of beta-secretase cleavage products, and these were ..
  3. Yan R, Han P, Miao H, Greengard P, Xu H. The transmembrane domain of the Alzheimer's beta-secretase (BACE1) determines its late Golgi localization and access to beta -amyloid precursor protein (APP) substrate. J Biol Chem. 2001;276:36788-96 pubmed
    ..beta-Secretase was recently identified as a novel membrane-bound aspartyl protease, named BACE1, Asp2, or memapsin 2. Employing confocal microscopy and subcellular fractionation, we have found that BACE1 is largely situated in ..
  4. Herskowitz J, Feng Y, Mattheyses A, Hales C, Higginbotham L, Duong D, et al. Pharmacologic inhibition of ROCK2 suppresses amyloid-? production in an Alzheimer's disease mouse model. J Neurosci. 2013;33:19086-98 pubmed publisher
    ..kinase activity, using an isoform-selective small molecule (SR3677), suppressed ?-site APP cleaving enzyme 1 (BACE1) enzymatic action and diminished production of A? in AD mouse brain...
  5. Schöbel S, Neumann S, Hertweck M, Dislich B, Kuhn P, Kremmer E, et al. A novel sorting nexin modulates endocytic trafficking and alpha-secretase cleavage of the amyloid precursor protein. J Biol Chem. 2008;283:14257-68 pubmed publisher
  6. Mamada N, Tanokashira D, Hosaka A, Kametani F, Tamaoka A, Araki W. Amyloid β-protein oligomers upregulate the β-secretase, BACE1, through a post-translational mechanism involving its altered subcellular distribution in neurons. Mol Brain. 2015;8:73 pubmed publisher
    Site amyloid precursor protein cleaving enzyme 1 (BACE1) is a membrane-bound aspartyl protease that initiates amyloid β-protein (Aβ) generation...
  7. Angeletti B, Waldron K, Freeman K, Bawagan H, Hussain I, Miller C, et al. BACE1 cytoplasmic domain interacts with the copper chaperone for superoxide dismutase-1 and binds copper. J Biol Chem. 2005;280:17930-7 pubmed
    ..The first step in the generation of Abeta is cleavage of amyloid precursor protein by the aspartic protease BACE1. Here we show that BACE1 interacts with CCS (the copper chaperone for superoxide dismutase-1 (SOD1)) through ..
  8. Vetrivel K, Cheng H, Kim S, Chen Y, Barnes N, Parent A, et al. Spatial segregation of gamma-secretase and substrates in distinct membrane domains. J Biol Chem. 2005;280:25892-900 pubmed
  9. Vetrivel K, Meckler X, Chen Y, Nguyen P, Seidah N, Vassar R, et al. Alzheimer disease Abeta production in the absence of S-palmitoylation-dependent targeting of BACE1 to lipid rafts. J Biol Chem. 2009;284:3793-803 pubmed publisher
    ..beta-amyloid (Abeta) peptides are generated via sequential proteolysis of amyloid precursor protein (APP) by BACE1 and gamma-secretase. A subset of BACE1 localizes to cholesterol-rich membrane microdomains, termed lipid rafts...

More Information

Publications53

  1. Rogers G, Edelman G, Mauro V. Differential utilization of upstream AUGs in the beta-secretase mRNA suggests that a shunting mechanism regulates translation. Proc Natl Acad Sci U S A. 2004;101:2794-9 pubmed
    beta-Secretase [also known as the beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1)] is an enzyme involved in the production of A beta-amyloid plaques in the brains of patients with Alzheimer's disease...
  2. Ding Y, Ko M, Pehar M, KOTCH F, Peters N, Luo Y, et al. Biochemical inhibition of the acetyltransferases ATase1 and ATase2 reduces ?-secretase (BACE1) levels and A? generation. J Biol Chem. 2012;287:8424-33 pubmed publisher
    The cellular levels of ?-site APP cleaving enzyme 1 (BACE1), the rate-limiting enzyme for the generation of the Alzheimer disease (AD) amyloid ?-peptide (A?), are tightly regulated by two ER-based acetyl-CoA:lysine acetyltransferases, ..
  3. Kametaka S, Shibata M, Moroe K, Kanamori S, Ohsawa Y, Waguri S, et al. Identification of phospholipid scramblase 1 as a novel interacting molecule with beta -secretase (beta -site amyloid precursor protein (APP) cleaving enzyme (BACE)). J Biol Chem. 2003;278:15239-45 pubmed
    beta-Site amyloid precursor protein (APP)-cleaving enzyme (BACE) is an integral membrane aspartic proteinase responsible for beta-site processing of APP, and its cytoplasmic region composed of 24 amino acid residues has been shown to be ..
  4. Nural Guvener H, Mutlu N, Gaballa M. BACE1 levels are elevated in congestive heart failure. Neurosci Lett. 2013;532:7-11 pubmed publisher
    ..To address this issue, we investigated microglia activation; levels of BACE1, the key rate-limiting enzyme involved in the pathogenesis of AD; and VEGF levels in the hippocampus and cortex ..
  5. Sannerud R, Declerck I, Peric A, Raemaekers T, Menendez G, Zhou L, et al. ADP ribosylation factor 6 (ARF6) controls amyloid precursor protein (APP) processing by mediating the endosomal sorting of BACE1. Proc Natl Acad Sci U S A. 2011;108:E559-68 pubmed publisher
    ..are generated through the sequential cleavage of amyloid precursor protein (APP) by ?-site APP cleaving enzyme 1 (BACE1) and ?-secretase...
  6. Zhiyou C, Yong Y, Shanquan S, Jun Z, Liangguo H, Ling Y, et al. Upregulation of BACE1 and beta-amyloid protein mediated by chronic cerebral hypoperfusion contributes to cognitive impairment and pathogenesis of Alzheimer's disease. Neurochem Res. 2009;34:1226-35 pubmed publisher
    ..To investigate expression of APP, BACE1 and A beta in the hippocampus of BCCAO rats and study pathophysiological mechanism of AD from CCH...
  7. Zhang S, Wang Z, Cai F, Zhang M, Wu Y, Zhang J, et al. BACE1 Cleavage Site Selection Critical for Amyloidogenesis and Alzheimer's Pathogenesis. J Neurosci. 2017;37:6915-6925 pubmed publisher
    ..Under normal conditions, ?-site APP cleaving enzyme 1 (BACE1) cleaves APP at minor Asp1 site to generate C99 for amyloid ? protein (A?) production, and ..
  8. Guglielmotto M, Aragno M, Autelli R, Giliberto L, Novo E, Colombatto S, et al. The up-regulation of BACE1 mediated by hypoxia and ischemic injury: role of oxidative stress and HIF1alpha. J Neurochem. 2009;108:1045-56 pubmed publisher
    ..Specifically, hypoxia significantly increases beta-site APP cleaving enzyme (BACE1) gene transcription through the over-expression of hypoxia inducible factor 1alpha, resulting in increased BACE1 ..
  9. John B, Meister M, Banning A, Tikkanen R. Flotillins bind to the dileucine sorting motif of ?-site amyloid precursor protein-cleaving enzyme 1 and influence its endosomal sorting. FEBS J. 2014;281:2074-87 pubmed publisher
    The ?-site amyloid precursor protein-cleaving enzyme 1 (BACE1) is a protease that participates in the amyloidogenic cleavage of the Alzheimer amyloid precursor protein...
  10. Blasko I, Beer R, Bigl M, Apelt J, Franz G, Rudzki D, et al. Experimental traumatic brain injury in rats stimulates the expression, production and activity of Alzheimer's disease beta-secretase (BACE-1). J Neural Transm (Vienna). 2004;111:523-36 pubmed
    ..In this study we investigated the expression pattern of beta-secretase (BACE-1) in ipsi- or contralateral hippocampus and cortex following controlled cortical TBI in rats...
  11. De Pietri Tonelli D, Mihailovich M, Di Cesare A, Codazzi F, Grohovaz F, Zacchetti D. Translational regulation of BACE-1 expression in neuronal and non-neuronal cells. Nucleic Acids Res. 2004;32:1808-17 pubmed
    As the main beta-secretase of the central nervous system, BACE-1 is a key protein in the pathogenesis of Alzheimer's disease. Excessive expression of the protein might cause an overproduction of the neurotoxic beta-amyloid peptide...
  12. Sugimoto I, Futakawa S, Oka R, Ogawa K, Marth J, Miyoshi E, et al. Beta-galactoside alpha2,6-sialyltransferase I cleavage by BACE1 enhances the sialylation of soluble glycoproteins. A novel regulatory mechanism for alpha2,6-sialylation. J Biol Chem. 2007;282:34896-903 pubmed
    b>BACE1 (beta-site amyloid precursor protein-cleaving enzyme-1) is a membrane-bound aspartic protease that cleaves amyloid precursor protein to produce a neurotoxic peptide, amyloid beta-peptide, and has been implicated in triggering the ..
  13. Zhang H, Gao Y, Dai Z, Meng T, Tu S, Yan Y. IGF-1 reduces BACE-1 expression in PC12 cells via activation of PI3-K/Akt and MAPK/ERK1/2 signaling pathways. Neurochem Res. 2011;36:49-57 pubmed publisher
    ..Little is known about the relationship between IGF-1 and ?-site amyloid precursor protein cleaving enzyme 1 (BACE-1), the protease essential for the production of ?-amyloid peptides (A?)...
  14. Guglielmotto M, Aragno M, Tamagno E, Vercellinatto I, Visentin S, Medana C, et al. AGEs/RAGE complex upregulates BACE1 via NF-?B pathway activation. Neurobiol Aging. 2012;33:196.e13-27 pubmed publisher
    ..diabetes and AD, the effect of 2 AGEs, pentosidine and glyceraldehydes-derived pyridinium (GLAP), was studied on BACE1 expression both in vivo, in streptozotocin treated rats, and in vitro in differentiated neuroblastoma cells...
  15. Urmoneit B, Reinsch C, Turner J, Czech C, Beyreuther K, Dyrks T. Inhibition of beta A4 production by specific modulation of beta-secretase activity. J Mol Neurosci. 1995;6:23-32 pubmed
    ..This provides experimental evidence for the intracellular localization of gamma-secretase activity and beta A4 generation. ..
  16. Lange Dohna C, Zeitschel U, Gaunitz F, Perez Polo J, Bigl V, Rossner S. Cloning and expression of the rat BACE1 promoter. J Neurosci Res. 2003;73:73-80 pubmed
    ..brains of Alzheimer's disease patients, requires the enzymatic activity of the beta-site APP-cleaving enzyme 1 (BACE1). We report the cloning and sequence of a 1...
  17. Hoffmeister A, Dietz G, Zeitschel U, Mossner J, Rossner S, Stahl T. BACE1 is a newly discovered protein secreted by the pancreas which cleaves enteropeptidase in vitro. JOP. 2009;10:501-6 pubmed
    Activity of beta-site APP-cleaving enzyme1 (BACE1) is required for the generation of beta-amyloid peptides, the principal constituents of plaques in the brains of patients with Alzheimer's disease...
  18. Zhang X, Huang X, Fang C, Li Q, Cui J, Sun J, et al. miR-124 Regulates the Expression of BACE1 in the Hippocampus Under Chronic Cerebral Hypoperfusion. Mol Neurobiol. 2017;54:2498-2506 pubmed publisher
    ..nervous system-specific miRNAs, and one of its target genes is ?-site amyloid precursor protein cleaving enzyme 1 (BACE1)...
  19. Yan X, Xiong K, Luo X, Struble R, Clough R. beta-Secretase expression in normal and functionally deprived rat olfactory bulbs: inverse correlation with oxidative metabolic activity. J Comp Neurol. 2007;501:52-69 pubmed
    ..beta-Secretase (BACE) is a prerequisite for amyloidogenesis, and it is up-regulated in sporadic AD...
  20. Martisova E, Solas M, Gerenu G, Milagro F, Campion J, Ramirez M. Mechanisms involved in BACE upregulation associated to stress. Curr Alzheimer Res. 2012;9:822-9 pubmed
    ..of the present work was to study a purported involvement of stress in amyloid pathology through the modulation of BACE expression...
  21. Qin X, Wang Y, Paudel H. Early Growth Response 1 (Egr-1) Is a Transcriptional Activator of ?-Secretase 1 (BACE-1) in the Brain. J Biol Chem. 2016;291:22276-22287 pubmed
    ..A? is generated by a sequential cleavage of amyloid precursor protein (APP) by ?-secretase 1 (BACE-1) followed by ?-secretase. BACE-1 cleavage of APP is the committed step in A? synthesis...
  22. Kocki J, Ułamek Kozioł M, Bogucka Kocka A, Januszewski S, Jabłoński M, Gil Kulik P, et al. Dysregulation of Amyloid-β Protein Precursor, β-Secretase, Presenilin 1 and 2 Genes in the Rat Selectively Vulnerable CA1 Subfield of Hippocampus Following Transient Global Brain Ischemia. J Alzheimers Dis. 2015;47:1047-56 pubmed publisher
    ..Our data demonstrate that brain ischemia activates delayed neuronal death in hippocampus in an AβPP-dependent manner, thus defining a new and important mode of ischemic cell death. ..
  23. Lahiri D, Maloney B, Ge Y. Functional domains of the BACE1 and BACE2 promoters and mechanisms of transcriptional suppression of the BACE2 promoter in normal neuronal cells. J Mol Neurosci. 2006;29:65-80 pubmed
    ..Following identification of beta-APP cleaving enzyme (BACE1) as the beta-secretase, a homologous beta-secretase 2 (BACE2) was described...
  24. Buggia Prevot V, Sevalle J, Rossner S, Checler F. NFkappaB-dependent control of BACE1 promoter transactivation by Abeta42. J Biol Chem. 2008;283:10037-47 pubmed publisher
    ..Alzheimer disease are generated from the beta-amyloid precursor protein (betaAPP) by cleavages by beta-secretase BACE1 and by presenilin-dependent gamma-secretase activities...
  25. Rossner S, Fuchsbrunner K, Lange Dohna C, Hartlage Rübsamen M, Bigl V, Betz A, et al. Munc13-1-mediated vesicle priming contributes to secretory amyloid precursor protein processing. J Biol Chem. 2004;279:27841-4 pubmed
    ..We establish that, in addition to PKC, Munc13-1 significantly contributes to the regulation of secretory APP metabolism. ..
  26. Bettegazzi B, Mihailovich M, Di Cesare A, Consonni A, Macco R, Pelizzoni I, et al. ?-Secretase activity in rat astrocytes: translational block of BACE1 and modulation of BACE2 expression. Eur J Neurosci. 2011;33:236-43 pubmed publisher
    b>BACE1 and BACE2 are two closely related membrane-bound aspartic proteases. BACE1 is widely recognized as the neuronal ?-secretase that cleaves the amyloid-? precursor protein, thus allowing the production of amyloid-?, i.e...
  27. Kitazume S, Tachida Y, Oka R, Kotani N, Ogawa K, Suzuki M, et al. Characterization of alpha 2,6-sialyltransferase cleavage by Alzheimer's beta -secretase (BACE1). J Biol Chem. 2003;278:14865-71 pubmed
    b>BACE1 is a membrane-bound aspartic protease that cleaves the amyloid precursor protein (APP) at the beta-secretase site, a critical step in the Alzheimer disease pathogenesis...
  28. Kirschling C, Kolsch H, Frahnert C, Rao M, Maier W, Heun R. Polymorphism in the BACE gene influences the risk for Alzheimer's disease. Neuroreport. 2003;14:1243-6 pubmed
    ..Abeta is generated by cleavage of the amyloid precursor protein by beta- and gamma-secretases. BACE (beta-site APP cleaving enzyme) was identified as the beta-secretase...
  29. Pluta R, Kocki J, Ułamek Kozioł M, Petniak A, Gil Kulik P, Januszewski S, et al. Discrepancy in Expression of β-Secretase and Amyloid-β Protein Precursor in Alzheimer-Related Genes in the Rat Medial Temporal Lobe Cortex Following Transient Global Brain Ischemia. J Alzheimers Dis. 2016;51:1023-31 pubmed publisher
    ..Finally, the ischemia-induced gene changes may play a key role in a late and slow onset of Alzheimer-type pathology. ..
  30. Kim D, Carey B, Wang H, Ingano L, Binshtok A, Wertz M, et al. BACE1 regulates voltage-gated sodium channels and neuronal activity. Nat Cell Biol. 2007;9:755-64 pubmed
    b>BACE1 activity is significantly increased in the brains of Alzheimer's disease patients, potentially contributing to neurodegeneration...
  31. Kamal A, Almenar Queralt A, Leblanc J, Roberts E, Goldstein L. Kinesin-mediated axonal transport of a membrane compartment containing beta-secretase and presenilin-1 requires APP. Nature. 2001;414:643-8 pubmed
  32. Sachse C, Kim Y, Agsten M, Huth T, Alzheimer C, Kovacs D, et al. BACE1 and presenilin/?-secretase regulate proteolytic processing of KCNE1 and 2, auxiliary subunits of voltage-gated potassium channels. FASEB J. 2013;27:2458-67 pubmed publisher
    b>BACE1 and presenilin (PS)/?-secretase play a major role in Alzheimer's disease pathogenesis by regulating amyloid-? peptide generation...
  33. Singh A, Pati U. CHIP stabilizes amyloid precursor protein via proteasomal degradation and p53-mediated trans-repression of β-secretase. Aging Cell. 2015;14:595-604 pubmed publisher
    ..deposition of amyloid-beta Aβ, a proteolytic cleavage of amyloid precursor protein (APP) by β-secretase/BACE1, forms senile plaque in the brain...
  34. Xie H, Zhao Y, Zhou Y, Liu L, Liu Y, Wang D, et al. MiR-9 Regulates the Expression of BACE1 in Dementia Induced by Chronic Brain Hypoperfusion in Rats. Cell Physiol Biochem. 2017;42:1213-1226 pubmed publisher
    ..Western blot and immunofluorescence were employed to detect the expression of ?-site APP cleaving enzyme 1 (BACE1) and c-AMP response element-binding protein (CREB)...
  35. He W, Hu J, Xia Y, Yan R. ?-site amyloid precursor protein cleaving enzyme 1(BACE1) regulates Notch signaling by controlling the cleavage of Jagged 1 (Jag1) and Jagged 2 (Jag2) proteins. J Biol Chem. 2014;289:20630-7 pubmed
    b>BACE1 is a type I transmembrane aspartyl protease that cleaves amyloid precursor protein at the ?-secretase site to initiate the release of ?-amyloid peptide...
  36. Spoelgen R, von Arnim C, Thomas A, Peltan I, Koker M, Deng A, et al. Interaction of the cytosolic domains of sorLA/LR11 with the amyloid precursor protein (APP) and beta-secretase beta-site APP-cleaving enzyme. J Neurosci. 2006;26:418-28 pubmed
    ..both sorLA and, surprisingly, a sorLA tail construct inhibited APP cleavage in a beta-site APP-cleaving enzyme (BACE)-dependent manner...
  37. Pastorino L, Ikin A, Lamprianou S, Vacaresse N, Revelli J, Platt K, et al. BACE (beta-secretase) modulates the processing of APLP2 in vivo. Mol Cell Neurosci. 2004;25:642-9 pubmed
    b>BACE is an aspartyl protease that cleaves the amyloid precursor protein (APP) at the beta-secretase cleavage site and is involved in Alzheimer's disease...
  38. Yang H, Sun Z, Jiang Q, Shang Q, Xu J. [Effect of estrogen-depletion and 17beta-estradiol replacement therapy upon rat hippocampus beta-amyloid generation]. Zhonghua Yi Xue Za Zhi. 2009;89:2658-61 pubmed
    ..The effects of estrogen depletion and 17beta-estradiol replacement therapy upon beta-secretase (BACE1) and neprilysin (NEP) expression were also analyzed by Western blot...
  39. Wang H, Song L, Lee A, Laird F, Wong P, Lee H. Mossy fiber long-term potentiation deficits in BACE1 knock-outs can be rescued by activation of alpha7 nicotinic acetylcholine receptors. J Neurosci. 2010;30:13808-13 pubmed publisher
    Site amyloid precursor protein-cleaving enzyme 1 (BACE1)-the neuronal ?-secretase responsible for producing ?-amyloid (A?) peptides-emerged as one of the key therapeutic targets of Alzheimer's disease (AD)...
  40. Xiong K, Cai H, Luo X, Struble R, Clough R, Yan X. Mitochondrial respiratory inhibition and oxidative stress elevate beta-secretase (BACE1) proteins and activity in vivo in the rat retina. Exp Brain Res. 2007;181:435-46 pubmed
    ..Beta-secretase (BACE, i.e., BACE1), a prerequisite for Abeta genesis, is elevated in sporadic AD...
  41. Koh D, Mauro V. Reconciling contradictory reports regarding translation of BACE1 mRNA: initiation mechanism is altered by different expression systems. RNA Biol. 2009;6:54-8 pubmed
    We previously showed that translation from the rat BACE1 5' leader is cap-dependent and that four AUG codons (AUG1-4) in the 5' leader were bypassed, partially or completely, depending on the cell line...
  42. Patil S, Sheng L, Masserang A, Chan C. Palmitic acid-treated astrocytes induce BACE1 upregulation and accumulation of C-terminal fragment of APP in primary cortical neurons. Neurosci Lett. 2006;406:55-9 pubmed
    ..The present study examines the role of saturated fatty acid, palmitic acid (PA), in causing BACE1 upregulation and consequent amyloidogenic processing of beta-amyloid precursor protein (APP), one of the main ..
  43. Brambillaa A, Lonati E, Milani C, Rizzo A, Farina F, Botto L, et al. Ischemic conditions and ß-secretase activation: The impact of membrane cholesterol enrichment as triggering factor in rat brain endothelial cells. Int J Biochem Cell Biol. 2015;69:95-104 pubmed
    ..The latter, represents a detrimental event that may contribute to β-amyloid homeostasis impairment in the brain and to Alzheimer's disease-related BBB dysfunctions. ..
  44. Kitazume S, Nakagawa K, Oka R, Tachida Y, Ogawa K, Luo Y, et al. In vivo cleavage of alpha2,6-sialyltransferase by Alzheimer beta-secretase. J Biol Chem. 2005;280:8589-95 pubmed
    beta-Site amyloid precursor protein-cleaving enzyme 1 (BACE1) is a membrane-bound aspartic protease that cleaves amyloid precursor protein to produce a neurotoxic peptide, Abeta, and is implicated in triggering the pathogenesis of ..