Top

Published in:

Open Access 01-12-2017 | Review

Role of BACE1 in Alzheimer’s synaptic function

Authors: Brati Das, Riqiang Yan

Published in: Translational Neurodegeneration | Issue 1/2017

Abstract

Alzheimer’s disease (AD) is the most common age-dependent disease of dementia, and there is currently no cure available. This hallmark pathologies of AD are the presence of amyloid plaques and neurofibrillary tangles. Although the exact etiology of AD remains a mystery, studies over the past 30 have shown that abnormal generation or accumulation of β-amyloid peptides (Aβ) is likely to be a predominant early event in AD pathological development. Aβ is generated from amyloid precursor protein (APP) via proteolytic cleavage by β-site APP cleaving enzyme 1 (BACE1). Chemical inhibition of BACE1 has been shown to reduce Aβ in animal studies and in human trials. While BACE1 inhibitors are currently being tested in clinical trials to treat AD patients, it is highly important to understand whether BACE1 inhibition will significantly impact cognitive functions in AD patients. This review summarizes the recent studies on BACE1 synaptic functions. This knowledge will help to guide the proper use of BACE1 inhibitors in AD therapy.

Musiek ES, Holtzman DM. Three dimensions of the amyloid hypothesis: time, space and ‘wingmen’. Nat Neurosci. 2015;18(6):800–6. doi:10.1038/nn.4018 CrossRefPubMedPubMedCentral

Selkoe DJ, Hardy J. The amyloid hypothesis of Alzheimer's disease at 25 years. EMBO Mol Med. 2016;8(6):595–608. doi:10.15252/emmm.201606210 CrossRefPubMedPubMedCentral

Malenka RC, Malinow R. Alzheimer's disease: recollection of lost memories. Nature. 2011;469(7328):44–5. doi:10.1038/469044a CrossRefPubMedPubMedCentral

Yan R, Fan Q, Zhou J, Vassar R. Inhibiting BACE1 to reverse synaptic dysfunctions in Alzheimer's disease. Neurosci Biobehav Rev. 2016;65:326–40. doi:10.1016/j.neubiorev.2016.03.025 CrossRefPubMedPubMedCentral

Haass C. Take five--BACE and the gamma-secretase quartet conduct Alzheimer's amyloid beta-peptide generation. EMBO J. 2004;23(3):483–8. doi:10.1038/sj.emboj.7600061 CrossRefPubMedPubMedCentral

Karch CM, Cruchaga C, Goate AM. Alzheimer's disease genetics: from the bench to the clinic. Neuron. 2014;83(1):11–26. doi:10.1016/j.neuron.2014.05.041 CrossRefPubMedPubMedCentral

Tanzi RE. The genetics of Alzheimer disease. Cold Spring Harb Perspect Med. 2012;2(10) doi:10.1101/cshperspect.a006296

Hussain I, Powell D, Howlett DR, Tew DG, Meek TD, Chapman C, et al. Identification of a novel aspartic protease (asp 2) as beta-secretase. Mol Cell Neurosci. 1999;14(6):419–27. doi:10.1006/mcne.1999.0811 CrossRefPubMed

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(4):1456–60.CrossRefPubMedPubMedCentral

10.

Sinha S, Anderson JP, Barbour R, Basi GS, Caccavello R, Davis D, et al. Purification and cloning of amyloid precursor protein beta-secretase from human brain. Nature. 1999;402(6761):537–40. doi:10.1038/990114 CrossRefPubMed

11.

Vassar R, Bennett BD, Babu-Khan S, Kahn S, Mendiaz EA, Denis P, et al. Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE. Science. 1999;286(5440):735–41.CrossRefPubMed

12.

Yan R, Bienkowski MJ, Shuck ME, Miao H, Tory MC, Pauley AM, et al. Membrane-anchored aspartyl protease with Alzheimer's disease beta-secretase activity. Nature. 1999;402(6761):533–7. doi:10.1038/990107 CrossRefPubMed

13.

Hebert LE, Scherr PA, Bienias JL, Bennett DA, Evans DA. Alzheimer disease in the US population: prevalence estimates using the 2000 census. Arch Neurol. 2003;60(8):1119–22. doi:10.1001/archneur.60.8.1119 CrossRefPubMed

14.

Alzheimer's A. 2016 Alzheimer's disease facts and figures. Alzheimers Dement. 2016;12(4):459–509CrossRef

15.

Holtzman DM, Morris JC, Goate AM. Alzheimer’s disease: the challenge of the second century. Sci Transl Med. 2011;3(77):77sr71. doi:10.1126/scitranslmed.3002369 CrossRef

16.

De Strooper B, Iwatsubo T, Wolfe MS. Presenilins and gamma-secretase: structure, function, and role in Alzheimer disease. Cold Spring Harb Perspect Med. 2012;2(1):a006304. doi:10.1101/cshperspect.a006304 CrossRefPubMedPubMedCentral

17.

Li Y, Bohm C, Dodd R, Chen F, Qamar S, Schmitt-Ulms G, et al. Structural biology of presenilin 1 complexes. Mol Neurodegener. 2014;9:59. doi:10.1186/1750-1326-9-59 CrossRefPubMedPubMedCentral

18.

Liu CC, Liu CC, Kanekiyo T, Xu H, Bu G. Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Nat Rev Neurol. 2013;9(2):106–18. doi:10.1038/nrneurol.2012.263 CrossRefPubMedPubMedCentral

19.

Saunders AM, Schmader K, Breitner JC, Benson MD, Brown WT, Goldfarb L, et al. Apolipoprotein E epsilon 4 allele distributions in late-onset Alzheimer's disease and in other amyloid-forming diseases. Lancet. 1993;342(8873):710–1.CrossRefPubMed

20.

Strittmatter WJ, Saunders AM, Schmechel D, Pericak-Vance M, Enghild J, Salvesen GS, Roses AD. Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc Natl Acad Sci U S A. 1993;90(5):1977–81.CrossRefPubMedPubMedCentral

21.

Holtzman DM, Herz J, Bu G. Apolipoprotein E and apolipoprotein E receptors: normal biology and roles in Alzheimer disease. Cold Spring Harb Perspect Med. 2012;2(3):a006312. doi:10.1101/cshperspect.a006312 CrossRefPubMedPubMedCentral

22.

Shibata M, Yamada S, Kumar SR, Calero M, Bading J, Frangione B, et al. Clearance of Alzheimer's amyloid-ss(1-40) peptide from brain by LDL receptor-related protein-1 at the blood-brain barrier. J Clin Invest. 2000;106(12):1489–99. doi:10.1172/JCI10498 CrossRefPubMedPubMedCentral

23.

Selkoe DJ. Alzheimer's disease is a synaptic failure. Science. 2002;298(5594):789–91. doi:10.1126/science.1074069 CrossRefPubMed

24.

Georgakopoulos A, Marambaud P, Efthimiopoulos S, Shioi J, Cui W, Li HC, et al. Presenilin-1 forms complexes with the cadherin/catenin cell-cell adhesion system and is recruited to intercellular and synaptic contacts. Mol Cell. 1999;4(6):893–902.CrossRefPubMed

25.

Bezprozvanny I, Hiesinger PR. The synaptic maintenance problem: membrane recycling, Ca2+ homeostasis and late onset degeneration. Mol Neurodegener. 2013;8:23. doi:10.1186/1750-1326-8-23 CrossRefPubMedPubMedCentral

26.

Ho A, Shen J. Presenilins in synaptic function and disease. Trends Mol Med. 2011;17(11):617–24. doi:10.1016/j.molmed.2011.06.002 CrossRefPubMedPubMedCentral

27.

Mattson MP. ER calcium and Alzheimer's disease: in a state of flux. Sci Signal. 2010;3(114):pe10. doi:10.1126/scisignal.3114pe10 CrossRefPubMedPubMedCentral

28.

Kazim SF, Iqbal K. Neurotrophic factor small-molecule mimetics mediated neuroregeneration and synaptic repair: emerging therapeutic modality for Alzheimer's disease. Mol Neurodegener. 2016;11(1):50. doi:10.1186/s13024-016-0119-y CrossRefPubMedPubMedCentral

29.

Pratt KG, Zimmerman EC, Cook DG, Sullivan JM. Presenilin 1 regulates homeostatic synaptic scaling through Akt signaling. Nat Neurosci. 2011;14(9):1112–4. doi:10.1038/nn.2893 CrossRefPubMedPubMedCentral

30.

Wasser CR, Masiulis I, Durakoglugil MS, Lane-Donovan C, Xian X, Beffert U, et al. Differential splicing and glycosylation of Apoer2 alters synaptic plasticity and fear learning. Sci Signal. 2014;7(353):ra113. doi:10.1126/scisignal.2005438 CrossRefPubMedPubMedCentral

31.

Gylys KH, Fein JA, Tan AM, Cole GM. Apolipoprotein E enhances uptake of soluble but not aggregated amyloid-beta protein into synaptic terminals. J Neurochem. 2003;84(6):1442–51.CrossRefPubMed

32.

Dumanis SB, Cha HJ, Song JM, Trotter JH, Spitzer M, Lee JY, et al. ApoE receptor 2 regulates synapse and dendritic spine formation. PLoS One. 2011;6(2):e17203. doi:10.1371/journal.pone.0017203 CrossRefPubMedPubMedCentral

33.

Forner S, Baglietto-Vargas D, Martini AC, Trujillo-Estrada L, LaFerla FM. Synaptic impairment in Alzheimer's disease: a Dysregulated symphony. Trends Neurosci. 2017;40(6):347–57. doi:10.1016/j.tins.2017.04.002 CrossRefPubMed

34.

Tu S, Okamoto S, Lipton SA, Xu H. Oligomeric Abeta-induced synaptic dysfunction in Alzheimer's disease. Mol Neurodegener. 2014;9:48. doi:10.1186/1750-1326-9-48 CrossRefPubMedPubMedCentral

35.

Audrain M, Fol R, Dutar P, Potier B, Billard JM, Flament J, et al. Alzheimer's disease-like APP processing in wild-type mice identifies synaptic defects as initial steps of disease progression. Mol Neurodegener. 2016;11:5. doi:10.1186/s13024-016-0070-y CrossRefPubMedPubMedCentral

36.

Coleman P, Federoff H, Kurlan R. A focus on the synapse for neuroprotection in Alzheimer disease and other dementias. Neurology. 2004;63(7):1155–62.CrossRefPubMed

37.

Kandalepas PC, Sadleir KR, Eimer WA, Zhao J, Nicholson DA, Vassar R. The Alzheimer's beta-secretase BACE1 localizes to normal presynaptic terminals and to dystrophic presynaptic terminals surrounding amyloid plaques. Acta Neuropathol. 2013;126(3):329–52. doi:10.1007/s00401-013-1152-3 CrossRefPubMedPubMedCentral

38.

Fukumoto H, Cheung BS, Hyman BT, Irizarry MC. Beta-secretase protein and activity are increased in the neocortex in Alzheimer disease. Arch Neurol. 2002;59(9):1381–9.CrossRefPubMed

39.

Holsinger RM, McLean CA, Beyreuther K, Masters CL, Evin G. Increased expression of the amyloid precursor beta-secretase in Alzheimer's disease. Ann Neurol. 2002;51(6):783–6. doi:10.1002/ana.10208 CrossRefPubMed

40.

Yang LB, Lindholm K, Yan R, Citron M, Xia W, Yang XL, et al. Elevated beta-secretase expression and enzymatic activity detected in sporadic Alzheimer disease. Nat Med. 2003;9(1):3–4. doi:10.1038/nm0103-3 CrossRefPubMed

41.

Almeida CG, Tampellini D, Takahashi RH, Greengard P, Lin MT, Snyder EM, Gouras GK. Beta-amyloid accumulation in APP mutant neurons reduces PSD-95 and GluR1 in synapses. Neurobiol Dis. 2005;20(2):187–98. doi:10.1016/j.nbd.2005.02.008 CrossRefPubMed

42.

Roselli F, Hutzler P, Wegerich Y, Livrea P, Almeida OF. Disassembly of shank and homer synaptic clusters is driven by soluble beta-amyloid(1-40) through divergent NMDAR-dependent signalling pathways. PLoS One. 2009;4(6):e6011. doi:10.1371/journal.pone.0006011 CrossRefPubMedPubMedCentral

43.

Roselli F, Tirard M, Lu J, Hutzler P, Lamberti P, Livrea P, et al. Soluble beta-amyloid1-40 induces NMDA-dependent degradation of postsynaptic density-95 at glutamatergic synapses. J Neurosci. 2005;25(48):11061–70. doi:10.1523/JNEUROSCI.3034-05.2005 CrossRefPubMed

44.

Wang LW, Berry-Kravis E, Hagerman RJ. Fragile X: leading the way for targeted treatments in autism. Neurotherapeutics. 2010;7(3):264–74. doi:10.1016/j.nurt.2010.05.005 CrossRefPubMedPubMedCentral

45.

Golovyashkina N, Penazzi L, Ballatore C, Smith AB 3rd, Bakota L, Brandt R. Region-specific dendritic simplification induced by Abeta, mediated by tau via dysregulation of microtubule dynamics: a mechanistic distinct event from other neurodegenerative processes. Mol Neurodegener. 2015;10:60. doi:10.1186/s13024-015-0049-0 CrossRefPubMedPubMedCentral

46.

Cai H, Wang Y, McCarthy D, Wen H, Borchelt DR, Price DL, Wong PC. BACE1 is the major beta-secretase for generation of Abeta peptides by neurons. Nat Neurosci. 2001;4(3):233–4. doi:10.1038/85064 CrossRefPubMed

47.

Luo Y, Bolon B, Kahn S, Bennett BD, Babu-Khan S, Denis P, et al. Mice deficient in BACE1, the Alzheimer's beta-secretase, have normal phenotype and abolished beta-amyloid generation. Nat Neurosci. 2001;4(3):231–2. doi:10.1038/85059 CrossRefPubMed

48.

Roberds SL, Anderson J, Basi G, Bienkowski MJ, Branstetter DG, Chen KS, McConlogue L. BACE knockout mice are healthy despite lacking the primary beta-secretase activity in brain: implications for Alzheimer's disease therapeutics. Hum Mol Genet. 2001;10(12):1317–1324.

49.

Laird FM, Cai H, Savonenko AV, Farah MH, 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(50):11693–709. doi:10.1523/JNEUROSCI.2766-05.2005 CrossRefPubMedPubMedCentral

50.

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(14):3639–49. doi:10.1523/JNEUROSCI.4396-06.2007 CrossRefPubMed

51.

Vassar R, Kuhn PH, Haass C, Kennedy ME, Rajendran L, Wong PC, Lichtenthaler SF. Function, therapeutic potential and cell biology of BACE proteases: current status and future prospects. J Neurochem. 2014;130(1):4–28. doi:10.1111/jnc.12715 CrossRefPubMedPubMedCentral

52.

Yan R. Stepping closer to treating Alzheimer's disease patients with BACE1 inhibitor drugs. Transl Neurodegener. 2016;5:13. doi:10.1186/s40035-016-0061-5 CrossRefPubMedPubMedCentral

53.

Yan R. Physiological functions of the beta-site Amyloid precursor protein cleaving enzyme 1 and 2. Front Mol Neurosci. 2017;10:97. doi:10.3389/fnmol.2017.00097 PubMedPubMedCentral

54.

Yan R, Vassar R. Targeting the beta secretase BACE1 for Alzheimer's disease therapy. Lancet Neurol. 2014;13(3):319–29. doi:10.1016/S1474-4422(13)70276-X CrossRefPubMedPubMedCentral

55.

Morris RG. D.O. Hebb: the Organization of Behavior, Wiley: New York; 1949. Brain Res Bull. 1999;50(5–6):437.CrossRefPubMed

56.

Wang H, Megill A, Wong PC, Kirkwood A, Lee HK. Postsynaptic target specific synaptic dysfunctions in the CA3 area of BACE1 knockout mice. PLoS One. 2014;9(3):e92279. doi:10.1371/journal.pone.0092279 CrossRefPubMedPubMedCentral

57.

Ohno M, Sametsky EA, Younkin LH, Oakley H, Younkin SG, Citron M, et al. BACE1 deficiency rescues memory deficits and cholinergic dysfunction in a mouse model of Alzheimer's disease. Neuron. 2004;41(1):27–33.CrossRefPubMed

58.

Tamayev R, Matsuda S, Arancio O, D'Adamio L. Beta- but not gamma-secretase proteolysis of APP causes synaptic and memory deficits in a mouse model of dementia. EMBO Mol Med. 2012;4(3):171–9. doi:10.1002/emmm.201100195 CrossRefPubMedPubMedCentral

59.

Citron M. Strategies for disease modification in Alzheimer's disease. Nat Rev Neurosci. 2004;5(9):677–85. doi:10.1038/nrn1495 CrossRefPubMed

60.

Vassar R. Beta-secretase (BACE) as a drug target for Alzheimer's disease. Adv Drug Deliv Rev. 2002;54(12):1589–602.CrossRefPubMed

61.

Dominguez D, Tournoy J, Hartmann D, Huth T, Cryns K, Deforce S, et al. Phenotypic and biochemical analyses of BACE1- and BACE2-deficient mice. J Biol Chem. 2005;280(35):30797–806. doi:10.1074/jbc.M505249200 CrossRefPubMed

62.

Manabe T, Wyllie DJ, Perkel DJ, Nicoll RA. Modulation of synaptic transmission and long-term potentiation: effects on paired pulse facilitation and EPSC variance in the CA1 region of the hippocampus. J Neurophysiol. 1993;70(4):1451–9.PubMed

63.

Wang H, Song L, Laird F, Wong PC, Lee HK. BACE1 knock-outs display deficits in activity-dependent potentiation of synaptic transmission at mossy fiber to CA3 synapses in the hippocampus. J Neurosci. 2008;28(35):8677–81. doi:10.1523/JNEUROSCI.2440-08.2008 CrossRefPubMedPubMedCentral

64.

Rozov A, Zilberter Y, Wollmuth LP, Burnashev N. Facilitation of currents through rat Ca2+−permeable AMPA receptor channels by activity-dependent relief from polyamine block. J Physiol. 1998;511(Pt 2):361–77.CrossRefPubMedPubMedCentral

65.

Puzzo D, Privitera L, Leznik E, Fa M, Staniszewski A, Palmeri A, Arancio O. Picomolar amyloid-beta positively modulates synaptic plasticity and memory in hippocampus. J Neurosci. 2008;28(53):14537–45. doi:10.1523/JNEUROSCI.2692-08.2008 CrossRefPubMedPubMedCentral

66.

Hu X, Fan Q, Hou H, Yan R. Neurological dysfunctions associated with altered BACE1-dependent Neuregulin-1 signaling. J Neurochem. 2016;136(2):234–49. doi:10.1111/jnc.13395 CrossRefPubMed

67.

Fleck D, Garratt AN, Haass C, Willem M. BACE1 dependent neuregulin processing: review. Curr Alzheimer Res. 2012;9(2):178–83.CrossRefPubMed

68.

Savonenko AV, Melnikova T, Laird FM, Stewart KA, Price DL, Wong PC. Alteration of BACE1-dependent NRG1/ErbB4 signaling and schizophrenia-like phenotypes in BACE1-null mice. Proc Natl Acad Sci U S A. 2008;105(14):5585–90. doi:10.1073/pnas.0710373105 CrossRefPubMedPubMedCentral

69.

Mei L, Nave KA. Neuregulin-ERBB signaling in the nervous system and neuropsychiatric diseases. Neuron. 2014;83(1):27–49. doi:10.1016/j.neuron.2014.06.007 CrossRefPubMedPubMedCentral

70.

Hu X, Hicks CW, He W, Wong P, Macklin WB, Trapp BD, Yan R. Bace1 modulates myelination in the central and peripheral nervous system. Nat Neurosci. 2006;9(12):1520–5. doi:10.1038/nn1797 CrossRefPubMed

71.

Fleck D, van Bebber F, Colombo A, Galante C, Schwenk BM, Rabe L, et al. Dual cleavage of neuregulin 1 type III by BACE1 and ADAM17 liberates its EGF-like domain and allows paracrine signaling. J Neurosci. 2013;33(18):7856–69. doi:10.1523/JNEUROSCI.3372-12.2013 CrossRefPubMed

72.

Stefansson H, Sigurdsson E, Steinthorsdottir V, Bjornsdottir S, Sigmundsson T, Ghosh S, et al. Neuregulin 1 and susceptibility to schizophrenia. Am J Hum Genet. 2002;71(4):877–92. doi:10.1086/342734 CrossRefPubMedPubMedCentral

73.

Harrison PJ, Law AJ. Neuregulin 1 and schizophrenia: genetics, gene expression, and neurobiology. Biol Psychiatry. 2006;60(2):132–40. doi:10.1016/j.biopsych.2005.11.002 CrossRefPubMed

74.

Del Pino I, Garcia-Frigola C, Dehorter N, Brotons-Mas JR, Alvarez-Salvado E, Martinez de Lagran M, et al. Erbb4 deletion from fast-spiking interneurons causes schizophrenia-like phenotypes. Neuron. 2013;79(6):1152–68. doi:10.1016/j.neuron.2013.07.010 CrossRefPubMed

75.

Fazzari P, Paternain AV, Valiente M, Pla R, Lujan R, Lloyd K, et al. Control of cortical GABA circuitry development by Nrg1 and ErbB4 signalling. Nature. 2010;464(7293):1376–80. doi:10.1038/nature08928 CrossRefPubMed

76.

Ting AK, Chen Y, Wen L, Yin DM, Shen C, Tao Y, et al. Neuregulin 1 promotes excitatory synapse development and function in GABAergic interneurons. J Neurosci. 2011;31(1):15–25. doi:10.1523/JNEUROSCI.2538-10.2011 CrossRefPubMedPubMedCentral

77.

Munro KM, Nash A, Pigoni M, Lichtenthaler SF, Gunnersen JM. Functions of the Alzheimer's disease protease BACE1 at the synapse in the central nervous system. J Mol Neurosci. 2016;60(3):305–15. doi:10.1007/s12031-016-0800-1 CrossRefPubMedPubMedCentral

78.

Kuhn PH, Koroniak K, Hogl S, Colombo A, Zeitschel U, Willem M, et al. Secretome protein enrichment identifies physiological BACE1 protease substrates in neurons. EMBO J. 2012;31(14):3157–68. doi:10.1038/emboj.2012.173 CrossRefPubMedPubMedCentral

79.

Pigoni M, Wanngren J, Kuhn PH, Munro KM, Gunnersen JM, Takeshima H, et al. Seizure protein 6 and its homolog seizure 6-like protein are physiological substrates of BACE1 in neurons. Mol Neurodegener. 2016;11(1):67. doi:10.1186/s13024-016-0134-z CrossRefPubMedPubMedCentral

80.

Shimizu-Nishikawa K, Kajiwara K, Kimura M, Katsuki M, Sugaya E. Cloning and expression of SEZ-6, a brain-specific and seizure-related cDNA. Brain Res Mol Brain Res. 1995;28(2):201–10.CrossRefPubMed

81.

Gunnersen JM, Kim MH, Fuller SJ, De Silva M, Britto JM, Hammond VE, et al. Sez-6 proteins affect dendritic arborization patterns and excitability of cortical pyramidal neurons. Neuron. 2007;56(4):621–39. doi:10.1016/j.neuron.2007.09.018 CrossRefPubMed

82.

Quitsch A, Berhorster K, Liew CW, Richter D, Kreienkamp HJ. Postsynaptic shank antagonizes dendrite branching induced by the leucine-rich repeat protein Densin-180. J Neurosci. 2005;25(2):479–87. doi:10.1523/JNEUROSCI.2699-04.2005 CrossRefPubMed

83.

Havik B, Rokke H, Dagyte G, Stavrum AK, Bramham CR, Steen VM. Synaptic activity-induced global gene expression patterns in the dentate gyrus of adult behaving rats: induction of immunity-linked genes. Neuroscience. 2007;148(4):925–36. doi:10.1016/j.neuroscience.2007.07.024 CrossRefPubMed

84.

Miyazaki T, Hashimoto K, Uda A, Sakagami H, Nakamura Y, Saito SY, Takeshima H. Disturbance of cerebellar synaptic maturation in mutant mice lacking BSRPs, a novel brain-specific receptor-like protein family. FEBS Lett. 2006;580(17):4057–4064. doi:10.1016/j.febslet.2006.06.043.

85.

Stutzer I, Selevsek N, Esterhazy D, Schmidt A, Aebersold R, & Stoffel M. Systematic proteomic analysis identifies beta-site amyloid precursor protein cleaving enzyme 2 and 1 (BACE2 and BACE1) substrates in pancreatic beta-cells. J Biol Chem. 2013;288(15):10536–10547. doi:10.1074/jbc.M112.444703.

86.

He W, Hu J, Xia Y, & Yan R. Beta-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(30):20630–20637. doi:10.1074/jbc.M114.579862.

87.

Hu X, He W, Luo X, Tsubota KE, Yan R. BACE1 regulates hippocampal astrogenesis via the Jagged1-notch pathway. Cell Rep. 2013;4(1):40–9. doi:10.1016/j.celrep.2013.06.005 CrossRefPubMedPubMedCentral

88.

Gaiano N, Fishell G. The role of notch in promoting glial and neural stem cell fates. Annu Rev Neurosci. 2002;25:471–90. doi:10.1146/annurev.neuro.25.030702.130823 CrossRefPubMed

89.

Morrison SJ, Perez SE, Qiao Z, Verdi JM, Hicks C, Weinmaster G, & Anderson DJ. Transient Notch activation initiates an irreversible switch from neurogenesis to gliogenesis by neural crest stem cells. Cell. 2000;101(5):499–510.

90.

Wilhelmsson U, Faiz M, de Pablo Y, Sjoqvist M, Andersson D, Widestrand A, et al. Astrocytes negatively regulate neurogenesis through the Jagged1-mediated notch pathway. Stem Cells. 2012;30(10):2320–9. doi:10.1002/stem.1196 CrossRefPubMed

91.

Alberi L, Liu S, Wang Y, Badie R, Smith-Hicks C, Wu J, et al. Activity-induced notch signaling in neurons requires arc/Arg3.1 and is essential for synaptic plasticity in hippocampal networks. Neuron. 2011;69(3):437–44. doi:10.1016/j.neuron.2011.01.004 CrossRefPubMedPubMedCentral

92.

Stump G, Durrer A, Klein AL, Lutolf S, Suter U, Taylor V. Notch1 and its ligands Delta-like and jagged are expressed and active in distinct cell populations in the postnatal mouse brain. Mech Dev. 2002;114(1–2):153–9.CrossRefPubMed

93.

Presente A, Boyles RS, Serway CN, de Belle JS, Andres AJ. Notch is required for long-term memory in drosophila. Proc Natl Acad Sci U S A. 2004;101(6):1764–8. doi:10.1073/pnas.0308259100 CrossRefPubMedPubMedCentral

94.

Clarke LE, Barres BA. Emerging roles of astrocytes in neural circuit development. Nat Rev Neurosci. 2013;14(5):311–21. doi:10.1038/nrn3484 CrossRefPubMedPubMedCentral

95.

Araque A, Parpura V, Sanzgiri RP, Haydon PG. Tripartite synapses: glia, the unacknowledged partner. Trends Neurosci. 1999;22(5):208–15.CrossRefPubMed

96.

Bushong EA, Martone ME, Jones YZ, Ellisman MH. Protoplasmic astrocytes in CA1 stratum radiatum occupy separate anatomical domains. J Neurosci. 2002;22(1):183–92.PubMed

97.

Halassa MM, Fellin T, Takano H, Dong JH, Haydon PG. Synaptic islands defined by the territory of a single astrocyte. J Neurosci. 2007;27(24):6473–7. doi:10.1523/JNEUROSCI.1419-07.2007 CrossRefPubMed

98.

Oberheim NA, Takano T, Han X, He W, Lin JH, Wang F, et al. Uniquely hominid features of adult human astrocytes. J Neurosci. 2009;29(10):3276–87. doi:10.1523/JNEUROSCI.4707-08.2009 CrossRefPubMedPubMedCentral

99.

Beattie EC, Stellwagen D, Morishita W, Bresnahan JC, Ha BK, Von Zastrow M, et al. Control of synaptic strength by glial TNFalpha. Science. 2002;295(5563):2282–5. doi:10.1126/science.1067859 CrossRefPubMed

100.

Benilova I, Gallardo R, Ungureanu AA, Castillo Cano V, Snellinx A, Ramakers M, et al. The Alzheimer disease protective mutation A2T modulates kinetic and thermodynamic properties of amyloid-beta (Abeta) aggregation. J Biol Chem. 2014;289(45):30977–89. doi:10.1074/jbc.M114.599027 CrossRefPubMedPubMedCentral

101.

Jonsson T, Atwal JK, Steinberg S, Snaedal J, Jonsson PV, Bjornsson S, et al. A mutation in APP protects against Alzheimer's disease and age-related cognitive decline. Nature. 2012;488(7409):96–9. doi:10.1038/nature11283 CrossRefPubMed

102.

Maloney JA, Bainbridge T, Gustafson A, Zhang S, Kyauk R, Steiner P, et al. Molecular mechanisms of Alzheimer disease protection by the A673T allele of amyloid precursor protein. J Biol Chem. 2014;289(45):30990–1000. doi:10.1074/jbc.M114.589069 CrossRefPubMedPubMedCentral

103.

Kennedy ME, Stamford AW, Chen X, Cox K, Cumming JN, Dockendorf MF, et al. The BACE1 inhibitor verubecestat (MK-8931) reduces CNS beta-amyloid in animal models and in Alzheimer's disease patients. Sci Transl Med. 2016;8(363):363ra150. doi:10.1126/scitranslmed.aad9704 CrossRefPubMed

Title: Role of BACE1 in Alzheimer’s synaptic function
Authors: Brati Das
Riqiang Yan
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: Translational Neurodegeneration / Issue 1/2017
Electronic ISSN: 2047-9158
DOI: https://doi.org/10.1186/s40035-017-0093-5

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Role of BACE1 in Alzheimer’s synaptic function

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2017

Mini-review on initiatives to interfere with the propagation and clearance of alpha-synuclein in Parkinson’s disease

Pathological correlations between traumatic brain injury and chronic neurodegenerative diseases

Factors predicting the instant effect of motor function after subthalamic nucleus deep brain stimulation in Parkinson’s disease

Rest tremor revisited: Parkinson’s disease and other disorders

RNAi mechanisms in Huntington’s disease therapy: siRNA versus shRNA

Music therapy is a potential intervention for cognition of Alzheimer’s Disease: a mini-review