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BACE1 Physiological Functions May Limit Its Use as Therapeutic Target for Alzheimer's Disease

Barão, Soraia, Moechars, Diederik, Lichtenthaler, Stefan F., De Strooper, Bart·2016·Trends in Neurosciences
DOI 10.1016/j.tins.2016.01.003
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Abstract

The protease β-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) is required for the production of the amyloid-β (Aβ) peptide, which is central to the pathogenesis of Alzheimer's disease (AD). Chronic inhibition of this protease may temper amyloid production and cure or prevent AD. However, while BACE1 inhibitors are being pushed forward as drug candidates, a remarkable gap in knowledge on the physiological functions of BACE1 and its close homolog BACE2 becomes apparent. Here we discuss 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.

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  • Several phenotypic changes have been described in BACE1-/- mice, such as epileptic seizures, schizophrenic symptoms, increased mortality and altered insulin metabolism.

    “Moreover, several phenotypic changes were described in BACE1-/- mice, such as epileptic seizures, schizophrenic symptoms, increased mortality and altered insulin metabolism, but most of the BACE1 substrates contributing to these phenotypes still need to be determined [13].”

    From Seizure protein 6 and its homolog seizure 6-like protein are physiological substrates of BACE1 in neurons (2016) · cites this paper as [13]

  • BACE1 is a major drug target in AD, but has additional substrates and thus contributes to various biological processes, which may limit its therapeutic potential.

    “BACE1 is a major drug target in AD, but has additional substrates and thus contributes to various biological processes [1, 13], which may limit its therapeutic potential.”

    From Seizure protein 6 and its homolog seizure 6-like protein are physiological substrates of BACE1 in neurons (2016) · cites this paper as [13]

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Research works printed but not linked: 70

  1. Luo, 2001, Mice deficient in BACE1, the Alzheimer's β-secretase, have normal phenotype and abolished β-amyloid generation, Nat. Neurosci., 4, 231, 10.1038/85059 · DOI · Paper page
  2. Di Fede, 2009, A recessive mutation in the APP gene with dominant-negative effect on amyloidogenesis, Science, 323, 1473, 10.1126/science.1168979 · DOI
  3. Benilova, 2014, The Alzheimer disease protective mutation A2T modulates kinetic and thermodynamic properties of amyloid-β (Aβ) aggregation, J. Biol. Chem., 289, 30977, 10.1074/jbc.M114.599027 · DOI
  4. Zhao, 2007, Beta-site amyloid precursor protein cleaving enzyme 1 levels become elevated in neurons around amyloid plaques: implications for Alzheimer's disease pathogenesis, J. Neurosci., 27, 3639, 10.1523/JNEUROSCI.4396-06.2007 · DOI · Paper page
  5. Yang, 2003, Elevated β-secretase expression and enzymatic activity detected in sporadic Alzheimer disease, Nat. Med., 9, 3, 10.1038/nm0103-3 · DOI · Paper page
  6. Vassar, 2014, Function, therapeutic potential and cell biology of BACE proteases: current status and future prospects, J. Neurochem., 130, 4, 10.1111/jnc.12715 · DOI · Paper page
  7. Kizuka, 2015, An aberrant sugar modification of BACE1 blocks its lysosomal targeting in Alzheimer's disease, EMBO Mol. Med., 7, 175, 10.15252/emmm.201404438 · DOI · Paper page
  8. Akasaka-Manya, 2010, Protective effect of N-glycan bisecting GlcNAc residues on β-amyloid production in Alzheimer's disease, Glycobiology, 20, 99, 10.1093/glycob/cwp152 · DOI
  9. Bhattacharyya, 2002, Truncated, inactive N-acetylglucosaminyltransferase III (GlcNAc-TIII) induces neurological and other traits absent in mice that lack GlcNAc-TIII, J. Biol. Chem., 277, 26300, 10.1074/jbc.M202276200 · DOI
  10. Rajendran, 2012, Membrane trafficking pathways in Alzheimer's disease, Traffic, 13, 759, 10.1111/j.1600-0854.2012.01332.x · DOI · Paper page
  11. Cataldo, 2000, Endocytic pathway abnormalities precede amyloid β deposition in sporadic Alzheimer's disease and Down syndrome, Am. J. Pathol., 157, 277, 10.1016/S0002-9440(10)64538-5 · DOI · Paper page
  12. Ginsberg, 2010, Microarray analysis of hippocampal CA1 neurons implicates early endosomal dysfunction during Alzheimer's disease progression, Biol. Psychiatry, 68, 885, 10.1016/j.biopsych.2010.05.030 · DOI · Paper page
  13. Jiang, 2010, Alzheimer's-related endosome dysfunction in Down syndrome is Aβ-independent but requires APP and is reversed by BACE-1 inhibition, Proc. Natl. Acad. Sci. U.S.A., 107, 1630, 10.1073/pnas.0908953107 · DOI
  14. Kim, 2015, Evidence that the rab5 effector APPL1 mediates APP-βCTF-induced dysfunction of endosomes in Down syndrome and Alzheimer's disease, Mol. Psychiatry
  15. Harrison, 2003, BACE1 (β-secretase) transgenic and knockout mice: identification of neurochemical deficits and behavioral changes, Mol. Cell. Neurosci., 24, 646, 10.1016/S1044-7431(03)00227-6 · DOI · Paper page
  16. Dominguez, 2005, Phenotypic and biochemical analyses of BACE1- and BACE2-deficient mice, J. Biol. Chem., 280, 30797, 10.1074/jbc.M505249200 · DOI
  17. Hu, 2006, Bace1 modulates myelination in the central and peripheral nervous system, Nat. Neurosci., 9, 1520, 10.1038/nn1797 · DOI · Paper page
  18. Hu, 2008, Genetic deletion of BACE1 in mice affects remyelination of sciatic nerves, FASEB J., 22, 2970, 10.1096/fj.08-106666 · DOI · Paper page
  19. Laird, 2005, BACE1, a major determinant of selective vulnerability of the brain to amyloid-β amyloidogenesis, is essential for cognitive, emotional, and synaptic functions, J. Neurosci., 25, 11693, 10.1523/JNEUROSCI.2766-05.2005 · DOI · Paper page
  20. Kobayashi, 2008, BACE1 gene deletion: impact on behavioral function in a model of Alzheimer's disease, Neurobiol. Aging, 29, 861, 10.1016/j.neurobiolaging.2007.01.002 · DOI · Paper page
  21. Wang, 2008, BACE1 knock-outs display deficits in activity-dependent potentiation of synaptic transmission at mossy fiber to CA3 synapses in the hippocampus, J. Neurosci., 28, 8677, 10.1523/JNEUROSCI.2440-08.2008 · DOI
  22. Filser, 2014, Pharmacological inhibition of BACE1 impairs synaptic plasticity and cognitive functions, Biol. Psychiatry, 77, 729, 10.1016/j.biopsych.2014.10.013 · DOI
  23. Hu, 2013, BACE1 regulates hippocampal astrogenesis via the Jagged1–Notch pathway, Cell Rep., 4, 40, 10.1016/j.celrep.2013.06.005 · DOI · Paper page
  24. Rajapaksha, 2011, The Alzheimer's β-secretase enzyme BACE1 is required for accurate axon guidance of olfactory sensory neurons and normal glomerulus formation in the olfactory bulb, Mol. Neurodegener., 6, 88, 10.1186/1750-1326-6-88 · DOI
  25. Cao, 2012, The precision of axon targeting of mouse olfactory sensory neurons requires the BACE1 protease, Sci. Rep., 2, 1, 10.1038/srep00231 · DOI
  26. Hitt, 2012, β-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., 287, 38408, 10.1074/jbc.M112.415505 · DOI · Paper page
  27. Barão, 2015, Antagonistic effects of BACE1 and APH1B-γ-secretase control axonal guidance by regulating growth cone collapse, Cell Rep., 12, 1367, 10.1016/j.celrep.2015.07.059 · DOI · Paper page
  28. Cheret, 2013, Bace1 and Neuregulin-1 cooperate to control formation and maintenance of muscle spindles, EMBO J., 32, 2015, 10.1038/emboj.2013.146 · DOI · Paper page
  29. Cai, 2012, β-Secretase (BACE1) inhibition causes retinal pathology by vascular dysregulation and accumulation of age pigment, EMBO Mol. Med., 4, 980, 10.1002/emmm.201101084 · DOI · Paper page
  30. Hitt, 2010, BACE1−/− mice exhibit seizure activity that does not correlate with sodium channel level or axonal localization, Mol. Neurodegener., 5, 31, 10.1186/1750-1326-5-31 · DOI · Paper page
  31. Kitazume, 2005, In vivo cleavage of α2,6-sialyltransferase by Alzheimer β-secretase, J. Biol. Chem., 280, 8589, 10.1074/jbc.M409417200 · DOI · Paper page
  32. Von Einem, 2010, The role of low-density receptor-related protein 1 (LRP1) as a competitive substrate of the amyloid precursor protein (APP) for BACE1, Exp. Neurol., 225, 85, 10.1016/j.expneurol.2010.05.017 · DOI
  33. Hemming, 2009, Identification of β-secretase (BACE1) substrates using quantitative proteomics, PLoS ONE, 4, e8477, 10.1371/journal.pone.0008477 · DOI
  34. Wong, 2005, β-Subunits of voltage-gated sodium channels are novel substrates of β-site amyloid precursor protein-cleaving enzyme (BACE1) and γ-secretase, J. Biol. Chem., 280, 23009, 10.1074/jbc.M414648200 · DOI
  35. Kim, 2007, BACE1 regulates voltage-gated sodium channels and neuronal activity, Nat. Cell Biol., 9, 755, 10.1038/ncb1602 · DOI
  36. Kuhn, 2012, Secretome protein enrichment identifies physiological BACE1 protease substrates in neurons, EMBO J., 31, 3157, 10.1038/emboj.2012.173 · DOI · Paper page
  37. Dislich, 2015, Label-free quantitative proteomics of mouse cerebrospinal fluid detects β-site APP cleaving enzyme (BACE1) protease substrates in vivo, Mol. Cell. Proteomics, 14, 2550, 10.1074/mcp.M114.041533 · DOI · Paper page
  38. Zhou, 2012, The neural cell adhesion molecules L1 and CHL1 are cleaved by BACE1 protease in vivo, J. Biol. Chem., 287, 25927, 10.1074/jbc.M112.377465 · DOI · Paper page
  39. Fazzari, 2014, Cell autonomous regulation of hippocampal circuitry via Aph1b-γ-secretase/Neuregulin 1 signalling, Elife, 10.7554/eLife.02196 · DOI
  40. Montag-Sallaz, 2002, Misguided axonal projections, neural cell adhesion molecule 180 mRNA upregulation, and altered behavior in mice deficient for the close homolog of L1, Mol. Cell. Biol., 22, 7967, 10.1128/MCB.22.22.7967-7981.2002 · DOI
  41. Castellani, 2000, Analysis of the L1-deficient mouse phenotype reveals cross-talk between Sema3A and L1 signaling pathways in axonal guidance, Neuron, 27, 237, 10.1016/S0896-6273(00)00033-7 · DOI
  42. Bagnard, 2001, Axonal surface molecules act in combination with semaphorin 3a during the establishment of corticothalamic projections, Cereb. Cortex, 11, 278, 10.1093/cercor/11.3.278 · DOI
  43. Sahay, 2005, Secreted semaphorins modulate synaptic transmission in the adult hippocampus, J. Neurosci., 25, 3613, 10.1523/JNEUROSCI.5255-04.2005 · DOI
  44. Wright, 2007, Close homolog of L1 and neuropilin 1 mediate guidance of thalamocortical axons at the ventral telencephalon, J. Neurosci., 27, 13667, 10.1523/JNEUROSCI.2888-07.2007 · DOI
  45. Bagri, 2003, Stereotyped pruning of long hippocampal axon branches triggered by retraction inducers of the semaphorin family, Cell, 113, 285, 10.1016/S0092-8674(03)00267-8 · DOI
  46. Urban, 2001, Revisiting the role of the hippocampal mossy fiber synapse, Hippocampus, 11, 408, 10.1002/hipo.1055 · DOI
  47. Kerjan, 2009, Mice lacking doublecortin and doublecortin-like kinase 2 display altered hippocampal neuronal maturation and spontaneous seizures, Proc. Natl. Acad. Sci. U.S.A., 106, 6766, 10.1073/pnas.0812687106 · DOI
  48. Bai, 2011, Presenilin-dependent receptor processing is required for axon guidance, Cell, 144, 106, 10.1016/j.cell.2010.11.053 · DOI
  49. Romi, 2014, ADAM metalloproteases promote a developmental switch in responsiveness to the axonal repellant Sema3A, Nat. Commun., 5, 4058, 10.1038/ncomms5058 · DOI
  50. Hessler, 2015, β-Secretase BACE1 regulates hippocampal and reconstituted M-currents in a β-subunit-like fashion, J. Neurosci., 35, 3298, 10.1523/JNEUROSCI.3127-14.2015 · DOI
  51. Avci, 2015, Clipping or extracting: two ways to membrane protein degradation, Trends Cell Biol., 25, 611, 10.1016/j.tcb.2015.07.003 · DOI
  52. Bennett, 2000, Expression analysis of BACE2 in brain and peripheral tissues, J. Biol. Chem., 275, 20647, 10.1074/jbc.M002688200 · DOI · Paper page
  53. Farzan, 2000, BACE2, a β-secretase homolog, cleaves at the β site and within the amyloid-β region of the amyloid-β precursor protein, Proc. Natl. Acad. Sci. U.S.A., 97, 9712, 10.1073/pnas.160115697 · DOI · Paper page
  54. Esterházy, 2011, Bace2 is a β cell-enriched protease that regulates pancreatic β cell function and mass, Cell Metab., 14, 365, 10.1016/j.cmet.2011.06.018 · DOI · Paper page
  55. Stutzer, 2013, Systematic proteomic analysis identifies β-site amyloid precursor protein cleaving enzyme 2 and 1 (BACE2 and BACE1) substrates in pancreatic β-cells, J. Biol. Chem., 288, 10536, 10.1074/jbc.M112.444703 · DOI · Paper page
  56. May, 2011, Robust central reduction of amyloid-β in humans with an orally available, non-peptidic β-secretase inhibitor, J. Neurosci., 31, 16507, 10.1523/JNEUROSCI.3647-11.2011 · DOI · Paper page
  57. Saftig, 1995, Mice deficient for the lysosomal proteinase cathepsin D exhibit progressive atrophy of the intestinal mucosa and profound destruction of lymphoid cells, EMBO J., 14, 3599, 10.1002/j.1460-2075.1995.tb00029.x · DOI
  58. Shacka, 2007, Cathepsin D deficiency induces persistent neurodegeneration in the absence of Bax-dependent apoptosis, J. Neurosci., 27, 2081, 10.1523/JNEUROSCI.5577-06.2007 · DOI
  59. Forman, 2012, The novel BACE inhibitor MK-8931 dramatically lowers cerebrospinal fluid Aβ peptides in healthy subjects following single- and multiple-dose administration, Alzheimers Demen., 8, P704, 10.1016/j.jalz.2012.05.1900 · DOI
  60. Forman, 2013, The novel BACE inhibitor MK-8931 dramatically lowers CSF β-amyloid in patients with mild-to-moderate Alzheimer's disease, Alzheimers Demen., 9, P139, 10.1016/j.jalz.2013.04.083 · DOI
  61. Verheijen, 2006, Detection of a soluble form of BACE-1 in human cerebrospinal fluid by a sensitive activity assay, Clin. Chem., 52, 1168, 10.1373/clinchem.2006.066720 · DOI
  62. Ewers, 2008, Increased CSF-BACE 1 activity is associated with ApoE-ɛ4 genotype in subjects with mild cognitive impairment and Alzheimer's disease, Brain, 131, 1252, 10.1093/brain/awn034 · DOI · Paper page
  63. Wu, 2008, Decrease in age-adjusted cerebrospinal fluid β-secretase activity in Alzheimer's subjects, Clin. Biochem., 41, 986, 10.1016/j.clinbiochem.2008.04.022 · DOI
  64. Barao, 2013, BACE1 levels correlate with phospho-tau levels in human cerebrospinal fluid, Curr. Alzheimer Res., 10, 671, 10.2174/15672050113109990138 · DOI
  65. Blennow, 1995, Tau protein in cerebrospinal fluid: a biochemical marker for axonal degeneration in Alzheimer disease?, Mol. Chem. Neuropathol., 26, 231, 10.1007/BF02815140 · DOI · Paper page
  66. Gonzales, 2011, Development of a specific ELISA to measure BACE1 levels in human tissues, J. Neurosci. Methods, 202, 70, 10.1016/j.jneumeth.2011.08.030 · DOI
  67. Zhang, 2015, δ-Secretase cleaves amyloid precursor protein and regulates the pathogenesis in Alzheimer's disease, Nat. Commun., 6, 8762, 10.1038/ncomms9762 · DOI · Paper page
  68. Reiner, 2013, Statins in the primary prevention of cardiovascular disease, Nat. Rev. Cardiol., 10, 453, 10.1038/nrcardio.2013.80 · DOI
  69. Ohno, 2007, BACE1 gene deletion prevents neuron loss and memory deficits in 5XFAD APP/PS1 transgenic mice, Neurobiol. Dis., 26, 134, 10.1016/j.nbd.2006.12.008 · DOI · Paper page
  70. De Strooper, 2012, Alzheimer's disease: a protective mutation, Nature, 488, 38, 10.1038/488038a · DOI

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Metadata

Authors
Barão, S., Moechars, D., Lichtenthaler, S. F., & De Strooper, B.
Venue
Trends in Neurosciences
Publisher
Elsevier BV
Published
2016-03
Volume
39
Issue
3
Pages
158-169
ISSN
0166-2236
DOI
10.1016/j.tins.2016.01.003
Cited by
158
References
18
Language
en
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)

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