BACE

Summary

Gene Symbol: BACE
Description: beta-secretase 1
Alias: ASP2, BACE, HSPC104, beta-secretase 1, APP beta-secretase, asp 2, aspartyl protease 2, beta-secretase 1 precursor variant 1, beta-site APP cleaving enzyme 1, beta-site APP-cleaving enzyme, beta-site amyloid beta A4 precursor protein-cleaving enzyme, memapsin-2, membrane-associated aspartic protease 2, transmembrane aspartic proteinase Asp2
Species: human
Products:     BACE

Top Publications

  1. Endres K, Postina R, Schroeder A, Mueller U, Fahrenholz F. Shedding of the amyloid precursor protein-like protein APLP2 by disintegrin-metalloproteinases. FEBS J. 2005;272:5808-20 pubmed
    ..Retinoic acid treatment of two neuroblastoma cell lines upregulated the expression of both APLP2 and ADAM10, thus leading to an increased release of soluble APLP2. ..
  2. von Arnim C, Kinoshita A, Peltan I, Tangredi M, Herl L, Lee B, et al. The low density lipoprotein receptor-related protein (LRP) is a novel beta-secretase (BACE1) substrate. J Biol Chem. 2005;280:17777-85 pubmed
    b>BACE is a transmembrane protease with beta-secretase activity that cleaves the amyloid precursor protein (APP)...
  3. Lin X, Koelsch G, Wu S, Downs D, Dashti A, Tang J. Human aspartic protease memapsin 2 cleaves the beta-secretase site of beta-amyloid precursor protein. Proc Natl Acad Sci U S A. 2000;97:1456-60 pubmed
    The cDNAs of two new human membrane-associated aspartic proteases, memapsin 1 and memapsin 2, have been cloned and sequenced...
  4. Vassar R, Kuhn P, Haass C, Kennedy M, Rajendran L, Wong P, et al. Function, therapeutic potential and cell biology of BACE proteases: current status and future prospects. J Neurochem. 2014;130:4-28 pubmed publisher
    ..This review highlights the recent progress in understanding cell biology, substrates, and functions of BACE proteases and discusses the therapeutic options and potential mechanism-based liabilities, in particular for BACE ..
  5. 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...
  6. Laird F, Cai H, Savonenko A, Farah M, He K, Melnikova T, et al. BACE1, a major determinant of selective vulnerability of the brain to amyloid-beta amyloidogenesis, is essential for cognitive, emotional, and synaptic functions. J Neurosci. 2005;25:11693-709 pubmed
  7. 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 ..
  8. Kobayashi D, Zeller M, Cole T, Buttini M, McConlogue L, Sinha S, et al. BACE1 gene deletion: impact on behavioral function in a model of Alzheimer's disease. Neurobiol Aging. 2008;29:861-73 pubmed
    ..These results suggest that while excess Abeta is functionally pathological, BACE1-mediated processing of APP and other substrates play a role in "normal" learning, memory and sensorimotor processes. ..
  9. Mowrer K, Wolfe M. Identification of a cis-acting element involved in the regulation of BACE1 mRNA alternative splicing. J Neurochem. 2009;109:1008-16 pubmed publisher
    ..Therefore, we have for the first time found evidence of a regulatory site involved in BACE1 alternative splicing, and these data indicate that minor sequence changes can dramatically alter BACE1 alternative splicing. ..

More Information

Publications83

  1. Okada H, Zhang W, Peterhoff C, Hwang J, Nixon R, Ryu S, et al. Proteomic identification of sorting nexin 6 as a negative regulator of BACE1-mediated APP processing. FASEB J. 2010;24:2783-94 pubmed publisher
    ..Our study identifies a novel cellular pathway by which SNX6 negatively modulates BACE1-mediated cleavage of APP. ..
  2. Coulson D, Beyer N, Quinn J, Brockbank S, Hellemans J, Irvine G, et al. BACE1 mRNA expression in Alzheimer's disease postmortem brain tissue. J Alzheimers Dis. 2010;22:1111-22 pubmed publisher
    ..This analysis suggested that increased BACE1 mRNA expression in remaining neuronal cells may contribute to the increased BACE1 protein levels and activity found in brain regions affected by AD. ..
  3. von Arnim C, von Einem B, Weber P, Wagner M, Schwanzar D, Spoelgen R, et al. Impact of cholesterol level upon APP and BACE proximity and APP cleavage. Biochem Biophys Res Commun. 2008;370:207-12 pubmed publisher
    Cleavage of APP by BACE is the first proteolytic step in the production of Amyloid beta (Abeta, which accumulates in senile plaques in Alzheimer's disease. BACE-cleavage of APP is thought to happen in endosomes...
  4. 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
    ..It thereby provides a novel avenue to interfere with A? production through a selective modulation of the distinct endosomal transport routes used by BACE1 or APP. ..
  5. Cai Y, Xiong K, Zhang X, Cai H, Luo X, Feng J, et al. ?-Secretase-1 elevation in aged monkey and Alzheimer's disease human cerebral cortex occurs around the vasculature in partnership with multisystem axon terminal pathogenesis and ?-amyloid accumulation. Eur J Neurosci. 2010;32:1223-38 pubmed publisher
    ..The data provide a mechanistic explanation for why senile plaques are present preferentially near the cerebral vasculature. ..
  6. Hemming M, Elias J, Gygi S, Selkoe D. Identification of beta-secretase (BACE1) substrates using quantitative proteomics. PLoS ONE. 2009;4:e8477 pubmed publisher
    ..These findings expand our understanding of the proteins and cellular processes that BACE1 may regulate, and suggest possible mechanisms of toxicity arising from chronic BACE1 inhibition. ..
  7. Jonas M, Costantini C, Puglielli L. PCSK9 is required for the disposal of non-acetylated intermediates of the nascent membrane protein BACE1. EMBO Rep. 2008;9:916-22 pubmed publisher
    ..In addition, Pcsk9(-/-) mice showed increased levels of BACE1 and Abeta in the brain. Finally, we found that nascent low-density lipoprotein receptor, a known substrate of PCSK9, is also acetylated. ..
  8. Li Y, Zhou W, Tong Y, He G, Song W. Control of APP processing and Abeta generation level by BACE1 enzymatic activity and transcription. FASEB J. 2006;20:285-92 pubmed
    ..Our data demonstrate that lower BACE transcription is responsible for the minority of APP undergoing the amyloidogenic pathway and relatively lower ..
  9. Kang E, Cameron A, Piazza F, Walker K, Tesco G. Ubiquitin regulates GGA3-mediated degradation of BACE1. J Biol Chem. 2010;285:24108-19 pubmed publisher
    ..These findings indicate that levels of GGA3 tightly and inversely regulate BACE1 levels via interaction with ubiquitin sorting machinery. ..
  10. Bennett B, Babu Khan S, Loeloff R, Louis J, Curran E, Citron M, et al. Expression analysis of BACE2 in brain and peripheral tissues. J Biol Chem. 2000;275:20647-51 pubmed
    Beta-site amyloid precursor protein cleaving enzyme (BACE) is a novel transmembrane aspartic protease that possesses all the known characteristics of the beta-secretase involved in Alzheimer's disease (Vassar, R., Bennett, B. D...
  11. Wong H, Sakurai T, Oyama F, Kaneko K, Wada K, Miyazaki H, et al. beta Subunits of voltage-gated sodium channels are novel substrates of beta-site amyloid precursor protein-cleaving enzyme (BACE1) and gamma-secretase. J Biol Chem. 2005;280:23009-17 pubmed
    ..These results may provide new insights into the underlying pathology of Alzheimer disease. ..
  12. 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
  13. Clarimon J, Bertranpetit J, Calafell F, Boada M, Tarraga L, Comas D. Association study between Alzheimer's disease and genes involved in Abeta biosynthesis, aggregation and degradation: suggestive results with BACE1. J Neurol. 2003;250:956-61 pubmed
    ..of these processes: proteolytic cleavage of the amyloid precursor protein by the beta-site APP cleaving enzyme (BACE), increased amyloid fibril formation by the activity of the acetylcholinesterase (ACHE gene), and degradation of ..
  14. Kodam A, Maulik M, Peake K, Amritraj A, Vetrivel K, Thinakaran G, et al. Altered levels and distribution of amyloid precursor protein and its processing enzymes in Niemann-Pick type C1-deficient mouse brains. Glia. 2010;58:1267-81 pubmed publisher
    ..These results, taken together, suggest that increased level and processing of APP may be associated with the development of pathology and/or degenerative events observed in Npc1(-/-) mouse brains. ..
  15. Mulder S, van der Flier W, Verheijen J, Mulder C, Scheltens P, Blankenstein M, et al. BACE1 activity in cerebrospinal fluid and its relation to markers of AD pathology. J Alzheimers Dis. 2010;20:253-60 pubmed publisher
    ..38, r=0.63, and r=0.65; all p< 0.05), but not with Abeta(42). These data suggest that increased BACE1 activity in CSF relates to AD pathology in the brain. ..
  16. Miners J, Morris S, Love S, Kehoe P. Accumulation of insoluble amyloid-? in down's syndrome is associated with increased BACE-1 and neprilysin activities. J Alzheimers Dis. 2011;23:101-8 pubmed publisher
    We previously reported age- and Alzheimer's disease (AD)-related increases in the activities of ?-secretase (BACE-1) and A?-degrading enzymes including neprilysin (NEP) and angiotensin-converting enzyme (ACE) in the frontal cortex...
  17. Kimura R, Devi L, Ohno M. Partial reduction of BACE1 improves synaptic plasticity, recent and remote memories in Alzheimer's disease transgenic mice. J Neurochem. 2010;113:248-61 pubmed publisher
    ..5XFAD mice. Therefore, our findings provide compelling evidence for beneficial effects of partially BACE1-inhibiting approaches on multiple forms of functional defects associated with AD. ..
  18. Christensen M, Zhou W, Qing H, Lehman A, Philipsen S, Song W. Transcriptional regulation of BACE1, the beta-amyloid precursor protein beta-secretase, by Sp1. Mol Cell Biol. 2004;24:865-74 pubmed
    ..promoter contains a functional Sp1 response element, and overexpression of the transcription factor Sp1 potentiates BACE gene expression and APP processing to generate Abeta. Furthermore, Sp1 knockout reduced BACE1 expression...
  19. Hussain I, Hawkins J, Shikotra A, Riddell D, Faller A, Dingwall C. Characterization of the ectodomain shedding of the beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1). J Biol Chem. 2003;278:36264-8 pubmed
    ..In addition, we show that the BACE1 sheddase is distinct from alpha-secretase and, importantly, that inhibition of BACE1 shedding does not influence amyloid precursor protein processing at the beta-site. ..
  20. Murphy T, Yip A, Brayne C, Easton D, Evans J, Xuereb J, et al. The BACE gene: genomic structure and candidate gene study in late-onset Alzheimer's disease. Neuroreport. 2001;12:631-4 pubmed
    ..Recently, the BACE gene, which encodes beta-secretase, the rate limiting enzyme in beta-amyloid formation, has been identified...
  21. Parkin E, Watt N, Hussain I, Eckman E, Eckman C, Manson J, et al. Cellular prion protein regulates beta-secretase cleavage of the Alzheimer's amyloid precursor protein. Proc Natl Acad Sci U S A. 2007;104:11062-7 pubmed
    ..In conclusion, this is a mechanism by which the cellular production of the neurotoxic Abeta is regulated by PrP(C) and may have implications for both Alzheimer's and prion diseases. ..
  22. Hussain I, Powell D, Howlett D, Tew D, Meek T, Chapman C, et al. Identification of a novel aspartic protease (Asp 2) as beta-secretase. Mol Cell Neurosci. 1999;14:419-27 pubmed
    ..Here we report that Asp 2, a novel transmembrane aspartic protease, has the key activities expected of beta-secretase...
  23. Yang L, Lindholm K, Yan R, Citron M, Xia W, Yang X, et al. Elevated beta-secretase expression and enzymatic activity detected in sporadic Alzheimer disease. Nat Med. 2003;9:3-4 pubmed
  24. Tamagno E, Bardini P, Obbili A, Vitali A, Borghi R, Zaccheo D, et al. Oxidative stress increases expression and activity of BACE in NT2 neurons. Neurobiol Dis. 2002;10:279-88 pubmed
    Recently an aspartyl protease with beta-secretase activity called BACE was identified. In the present paper we showed that BACE is modulated by the oxidative stress product 4-hydroxynonenal (HNE)...
  25. Walter J, Fluhrer R, Hartung B, Willem M, Kaether C, Capell A, et al. Phosphorylation regulates intracellular trafficking of beta-secretase. J Biol Chem. 2001;276:14634-41 pubmed
    beta-Secretase (BACE) is a transmembrane aspartyl protease, which generates the N terminus of Alzheimer's disease amyloid beta-peptide...
  26. Holsinger R, McLean C, Beyreuther K, Masters C, Evin G. Increased expression of the amyloid precursor beta-secretase in Alzheimer's disease. Ann Neurol. 2002;51:783-6 pubmed
    ..7-fold increase in protein expression of the beta-secretase enzyme BACE in the brain cortex of Alzheimer's disease patients as compared to age-matched controls...
  27. Cho H, Jin S, Son S, Kim Y, Hwang J, Hong H, et al. Constitutive JAK2/STAT1 activation regulates endogenous BACE1 expression in neurons. Biochem Biophys Res Commun. 2009;386:175-80 pubmed publisher
    ..Therefore, we propose that constitutive JAK2/STAT1 activation mediates endogenous BACE1 expression in neurons and that inhibition of JAK2/STAT1 signaling abrogates basal levels of BACE1 expression and Abeta generation. ..
  28. von Arnim C, Tangredi M, Peltan I, Lee B, Irizarry M, Kinoshita A, et al. Demonstration of BACE (beta-secretase) phosphorylation and its interaction with GGA1 in cells by fluorescence-lifetime imaging microscopy. J Cell Sci. 2004;117:5437-45 pubmed
    beta-Secretase (BACE) carries out the first of two proteolysis steps to generate the amyloid-beta peptides that accumulate in the senile plaques in Alzheimer's disease (AD)...
  29. Willem M, Lammich S, Haass C. Function, regulation and therapeutic properties of beta-secretase (BACE1). Semin Cell Dev Biol. 2009;20:175-82 pubmed publisher
    ..BACE1 is a primary target for Abeta lowering therapies, however the development of high affinity bio-available inhibitors has been a major challenge so far. ..
  30. Faghihi M, Modarresi F, Khalil A, Wood D, Sahagan B, Morgan T, et al. Expression of a noncoding RNA is elevated in Alzheimer's disease and drives rapid feed-forward regulation of beta-secretase. Nat Med. 2008;14:723-30 pubmed publisher
    ..In summary, we report that a long noncoding RNA is directly implicated in the increased abundance of Abeta 1-42 in Alzheimer's disease. ..
  31. Pastorino L, Ikin A, Nairn A, Pursnani A, Buxbaum J. The carboxyl-terminus of BACE contains a sorting signal that regulates BACE trafficking but not the formation of total A(beta). Mol Cell Neurosci. 2002;19:175-85 pubmed
    b>BACE (beta-site APP cleaving enzyme) has been recently proposed as the major aspartyl protease displaying beta secretase activity in neurons...
  32. Hitt B, Riordan S, Kukreja L, Eimer W, Rajapaksha T, Vassar R. ?-Site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1)-deficient mice exhibit a close homolog of L1 (CHL1) loss-of-function phenotype involving axon guidance defects. J Biol Chem. 2012;287:38408-25 pubmed publisher
    ..Our results imply the possibility that axon mis-targeting may occur in adult neurogenic and/or regenerating neurons as a result of chronic BACE1 inhibition and add a note of caution to BACE1 inhibitor development...
  33. He X, Zhu G, Koelsch G, Rodgers K, Zhang X, Tang J. Biochemical and structural characterization of the interaction of memapsin 2 (beta-secretase) cytosolic domain with the VHS domain of GGA proteins. Biochemistry. 2003;42:12174-80 pubmed
    b>Memapsin 2 (beta-secretase) is a membrane-associated aspartic protease that initiates the hydrolysis of beta-amyloid precursor protein (APP) leading to the production of amyloid-beta and the onset of Alzheimer's disease (AD)...
  34. Schmechel A, Strauss M, Schlicksupp A, Pipkorn R, Haass C, Bayer T, et al. Human BACE forms dimers and colocalizes with APP. J Biol Chem. 2004;279:39710-7 pubmed
    Beta-site APP-cleaving enzyme (BACE) is a membrane-bound aspartyl protease with no strict primary preference for cleavage...
  35. He X, Li F, Chang W, Tang J. GGA proteins mediate the recycling pathway of memapsin 2 (BACE). J Biol Chem. 2005;280:11696-703 pubmed
    b>Memapsin 2 (BACE, beta-secretase) is a membrane-associated aspartic protease that initiates the hydrolysis of beta-amyloid precursor protein (APP) leading to the production of amyloid-beta (A beta) and the progression of Alzheimer disease...
  36. Lichtenthaler S, Dominguez D, Westmeyer G, Reiss K, Haass C, Saftig P, et al. The cell adhesion protein P-selectin glycoprotein ligand-1 is a substrate for the aspartyl protease BACE1. J Biol Chem. 2003;278:48713-9 pubmed
    ..The cleavage occurred at a Leu-Ser peptide bond as identified by mass spectrometry using a synthetic peptide. We conclude that PSGL-1 is an additional substrate for BACE1. ..
  37. Velanac V, Unterbarnscheidt T, Hinrichs W, Gummert M, Fischer T, Rossner M, et al. Bace1 processing of NRG1 type III produces a myelin-inducing signal but is not essential for the stimulation of myelination. Glia. 2012;60:203-17 pubmed publisher
    ..Thus, BACE1 is not essential for the activation of NRG1 type III to promote myelination. Taken together, these findings suggest that multiple neuronal proteases collectively regulate NRG1 processing. ..
  38. Fukumoto H, Cheung B, Hyman B, Irizarry M. Beta-secretase protein and activity are increased in the neocortex in Alzheimer disease. Arch Neurol. 2002;59:1381-9 pubmed
    ..dependent on presenilin, and a beta-secretase cleavage by the aspartyl protease beta-site APP-cleaving enzyme (BACE)...
  39. Yan R, Bienkowski M, Shuck M, Miao H, Tory M, Pauley A, et al. Membrane-anchored aspartyl protease with Alzheimer's disease beta-secretase activity. Nature. 1999;402:533-7 pubmed
    ..Here we identify a new membrane-bound aspartyl protease (Asp2) with beta-secretase activity. The Asp2 gene is expressed widely in brain and other tissues...
  40. Sinha S, Anderson J, Barbour R, Basi G, Caccavello R, Davis D, et al. Purification and cloning of amyloid precursor protein beta-secretase from human brain. Nature. 1999;402:537-40 pubmed
    ..Cloning and expression of the enzyme reveals that human brain beta-secretase is a new membrane-bound aspartic proteinase. ..
  41. Gong B, Chen F, Pan Y, Arrieta Cruz I, Yoshida Y, Haroutunian V, et al. SCFFbx2-E3-ligase-mediated degradation of BACE1 attenuates Alzheimer's disease amyloidosis and improves synaptic function. Aging Cell. 2010;9:1018-31 pubmed publisher
    ..Our study is the first to suggest that promoting Fbx2 in the brain may represent a novel strategy for the treatment of AD. ..
  42. 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...
  43. Griffiths H, Whitehouse I, Baybutt H, Brown D, Kellett K, Jackson C, et al. Prion protein interacts with BACE1 protein and differentially regulates its activity toward wild type and Swedish mutant amyloid precursor protein. J Biol Chem. 2011;286:33489-500 pubmed publisher
    ..Thus, although PrP(C) exerts no control on cleavage of APP(Swe) by BACE1, it has a profound influence on the cleavage of APP(WT), suggesting that PrP(C) may be a key protective player against sporadic Alzheimer disease. ..
  44. Costantini C, Ko M, Jonas M, Puglielli L. A reversible form of lysine acetylation in the ER and Golgi lumen controls the molecular stabilization of BACE1. Biochem J. 2007;407:383-95 pubmed
    ..Site-directed mutagenesis indicates that lysine acetylation is necessary for nascent BACE1 to leave the ER and move ahead in the secretory pathway, and for the molecular stabilization of the protein. ..
  45. Huse J, Liu K, Pijak D, Carlin D, Lee V, Doms R. Beta-secretase processing in the trans-Golgi network preferentially generates truncated amyloid species that accumulate in Alzheimer's disease brain. J Biol Chem. 2002;277:16278-84 pubmed
    ..The beta-secretase enzyme beta-site amyloid precursor protein-cleaving enzyme (BACE) generates the N terminus of A beta by cleavage at either Asp(1) (beta-site) or Glu(11) (beta'-site), ultimately ..
  46. Shimizu H, Tosaki A, Kaneko K, Hisano T, Sakurai T, Nukina N. Crystal structure of an active form of BACE1, an enzyme responsible for amyloid beta protein production. Mol Cell Biol. 2008;28:3663-71 pubmed publisher
    ..These findings provide insight into a novel regulation of BACE1 activity and elucidate how BACE1 modulates its activity during cellular trafficking. ..
  47. Murayama K, Kametani F, Saito S, Kume H, Akiyama H, Araki W. Reticulons RTN3 and RTN4-B/C interact with BACE1 and inhibit its ability to produce amyloid beta-protein. Eur J Neurosci. 2006;24:1237-44 pubmed
    ..Because RTN3 and RTN4-B/C are substantially expressed in neural tissues, our findings suggest that they play important roles in the regulation of BACE1 function and Abeta production in the brain. ..
  48. Kandalepas P, Sadleir K, Eimer W, Zhao J, Nicholson D, Vassar R. The Alzheimer's ?-secretase BACE1 localizes to normal presynaptic terminals and to dystrophic presynaptic terminals surrounding amyloid plaques. Acta Neuropathol. 2013;126:329-52 pubmed publisher
    ..Elevated BACE1 and APP levels in plaque-associated presynaptic dystrophies could increase local peri-plaque A? generation and accelerate amyloid plaque growth in AD. ..
  49. 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
    ..BACE1, by cleaving beta2, thus regulates Na(v)1 alpha-subunit levels and controls cell-surface sodium current densities. BACE1 inhibitors may normalize membrane excitability in Alzheimer's disease patients with elevated BACE1 activity. ..
  50. Tyler S, Dawbarn D, Wilcock G, Allen S. alpha- and beta-secretase: profound changes in Alzheimer's disease. Biochem Biophys Res Commun. 2002;299:373-6 pubmed
    ..Eighty percent of Alzheimer brains examined had an increase in beta-secretase, a decrease in alpha-secretase, or both; which may account for the means by which the majority of people develop Alzheimer's disease. ..
  51. Koh Y, von Arnim C, Hyman B, Tanzi R, Tesco G. BACE is degraded via the lysosomal pathway. J Biol Chem. 2005;280:32499-504 pubmed
    ..A type I transmembrane aspartyl protease, BACE (beta-site APP cleaving enzyme), has been identified to be the beta-secretase...
  52. Westmeyer G, Willem M, Lichtenthaler S, Lurman G, Multhaup G, Assfalg Machleidt I, et al. Dimerization of beta-site beta-amyloid precursor protein-cleaving enzyme. J Biol Chem. 2004;279:53205-12 pubmed
    Cleavage of the beta-amyloid precursor protein (APP) by the aspartyl protease beta-site APP-cleaving enzyme (BACE) is the first step in the generation of the amyloid beta-peptide, which is deposited in the brain of Alzheimer's disease ..
  53. Yan R, Vassar R. Targeting the ? secretase BACE1 for Alzheimer's disease therapy. Lancet Neurol. 2014;13:319-29 pubmed publisher
    ..The potential of therapeutic BACE1 inhibition might prove to be a watershed in the treatment of Alzheimer's disease. ..
  54. Kandalepas P, Vassar R. Identification and biology of ?-secretase. J Neurochem. 2012;120 Suppl 1:55-61 pubmed publisher
    ..These data are crucial for predicting potential mechanism-based toxicity that would arise from inhibiting BACE1 for the treatment or prevention of AD. ..
  55. Li Q, Sudhof T. Cleavage of amyloid-beta precursor protein and amyloid-beta precursor-like protein by BACE 1. J Biol Chem. 2004;279:10542-50 pubmed
    Site-specific proteolysis of the amyloid-beta precursor protein (APP) by BACE 1 and gamma-secretase, a central event in Alzheimer disease, releases a large secreted extracellular fragment (called APP(S)), peptides of 40-43 residues ..
  56. von Einem B, Schwanzar D, Rehn F, Beyer A, Weber P, Wagner M, et al. The role of low-density receptor-related protein 1 (LRP1) as a competitive substrate of the amyloid precursor protein (APP) for BACE1. Exp Neurol. 2010;225:85-93 pubmed publisher
    ..In conclusion, our data suggest that--in addition to its role in APP trafficking--LRP1 affects APP processing by competing for cleavage by BACE1. ..
  57. Kitazume S, Tachida Y, Oka R, Nakagawa K, Takashima S, Lee Y, et al. Screening a series of sialyltransferases for possible BACE1 substrates. Glycoconj J. 2006;23:437-41 pubmed
    ..These results suggest that BACE1 expression affects glycosylation not only by directly cleaving glycosyltransferases but also by modifying the secretion of glycosyltransferases via some other mechanisms. ..
  58. 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 ..
  59. Wahle T, Prager K, Raffler N, Haass C, Famulok M, Walter J. GGA proteins regulate retrograde transport of BACE1 from endosomes to the trans-Golgi network. Mol Cell Neurosci. 2005;29:453-61 pubmed
    ..Our data indicate that GGA proteins are not only involved in the sorting at the TGN but also mediate the retrograde transport of cargo proteins from endosomes to the TGN. ..
  60. Ko M, Puglielli L. Two endoplasmic reticulum (ER)/ER Golgi intermediate compartment-based lysine acetyltransferases post-translationally regulate BACE1 levels. J Biol Chem. 2009;284:2482-92 pubmed publisher
    ..The biochemical characterization of the above events could lead to the identification of novel pharmacological strategies for the prevention of this form of dementia. ..
  61. Ahmed R, Holler C, Webb R, Li F, Beckett T, Murphy M. BACE1 and BACE2 enzymatic activities in Alzheimer's disease. J Neurochem. 2010;112:1045-53 pubmed publisher
    ..However, as both forms of BACE compete for the same substrate pool, even small changes in BACE2 activity could have consequences for human disease. ..
  62. Shiba T, Kametaka S, Kawasaki M, Shibata M, Waguri S, Uchiyama Y, et al. Insights into the phosphoregulation of beta-secretase sorting signal by the VHS domain of GGA1. Traffic. 2004;5:437-48 pubmed
    b>BACE (beta-site amyloid precursor protein cleaving enzyme, beta-secretase) is a type-I membrane protein which functions as an aspartic protease in the production of beta-amyloid peptide, a causative agent of Alzheimer's disease...
  63. 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
    ..Our results also suggest a functional role of KCNE cleavage in regulating voltage-gated potassium channels. ..
  64. He W, Lu Y, Qahwash I, Hu X, Chang A, Yan R. Reticulon family members modulate BACE1 activity and amyloid-beta peptide generation. Nat Med. 2004;10:959-65 pubmed
    ..Thus, changes in the expression of reticulon proteins in the human brain are likely to affect cellular amyloid-beta and the formation of amyloid plaques. ..
  65. Zhao J, Fu Y, Yasvoina M, Shao P, Hitt B, O CONNOR T, et al. Beta-site amyloid precursor protein cleaving enzyme 1 levels become elevated in neurons around amyloid plaques: implications for Alzheimer's disease pathogenesis. J Neurosci. 2007;27:3639-49 pubmed
    ..To distinguish between these possibilities, we analyzed BACE1 elevation using a highly specific BACE1 antibody, BACE-Cat1, made in BACE1-/- mice, which mount a robust anti-BACE1 immune response...
  66. Sun X, Bromley Brits K, Song W. Regulation of ?-site APP-cleaving enzyme 1 gene expression and its role in Alzheimer's disease. J Neurochem. 2012;120 Suppl 1:62-70 pubmed publisher
    ..Further studies on BACE1 gene expression regulation will greatly contribute to our understanding of AD pathogenesis and reveal potential novel approaches for AD prevention and drug development. ..
  67. Gruninger Leitch F, Schlatter D, Küng E, Nelböck P, Döbeli H. Substrate and inhibitor profile of BACE (beta-secretase) and comparison with other mammalian aspartic proteases. J Biol Chem. 2002;277:4687-93 pubmed
    The full-length and ectodomain forms of beta-site APP cleavage enzyme (BACE) have been cloned, expressed in Sf9 cells, and purified to homogeneity...
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