Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
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Advances in Clinical and Experimental Medicine

2019, vol. 28, nr 12, December, p. 1717–1722

doi: 10.17219/acem/110319

Publication type: review

Language: English

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Matrix metalloproteinase-3 in brain physiology and neurodegeneration

Anna Maria Lech1,2,D,E,F, Grzegorz Wiera2,D,E,F, Jerzy Władysław Mozrzymas2,D,E,F

1 Department of Molecular Physiology and Neurobiology, University of Wrocław, Poland

2 Laboratory of Neuroscience, Department of Biophysics, Wroclaw Medical University, Poland

Abstract

Structural and functional synapse reorganization is one of the key issues of learning and memory mechanisms. Specific proteases, called matrix metalloproteinases (MMPs), play a pivotal role during learning-related modification of neural circuits. Different types of MMPs modify the extracellular perisynaptic environment, leading to the plastic changes in the synapses. In recent years, there has been an increasing interest in the role played by matrix metalloproteinase-3 (MMP-3) in various processes occurring in the mammalian brain, both in physiological and pathological conditions. In this review, we discuss a crucial function of MMP-3 in synaptic plasticity, learning, neuronal development, as well as in neuroregeneration. We discuss the involvement of MMP-3 in synaptic long-term potentiation, which is likely to have a profound impact on experience-dependent learning. On the other hand, we also provide examples of deleterious actions of uncontrolled MMP-3 activity on the central nervous system (CNS) and its contribution to Alzheimer’s and Parkinson’s diseases (AD and PD). Since the molecular mechanisms controlled by MMP-3 have a profound and diverse impact on physiological and pathological brain functioning, their deep understanding may be crucial for the development of more specific methods for the treatment of neuropsychiatric diseases.

Key words

neuroplasticity, MMP-3, neurodegenerative diseases, learning and memory, long-term potentiation

References (60)

  1. Citri A, Malenka RC. Synaptic plasticity: Multiple forms, functions, and mechanisms. Neuropsychopharmacology. 2008;33(1):18–41.
  2. Uzunova G, Pallanti S, Hollander E. Excitatory/inhibitory imbalance in autism spectrum disorders: Implications for interventions and therapeutics. World J Biol Psychiatry. 2016;17(3):174–186.
  3. Canitano R, Pallagrosi M. Autism spectrum disorders and schizophrenia spectrum disorders: Excitation/inhibition imbalance and developmental trajectories. Front Psychiatry. 2017;8:1–7.
  4. Buckley AH, Holmes GL. Epilepsy and autism. Cold Spring Harb ­Perspect Med. 2016;6(4):a022749.
  5. Dityatev A, Schachner M. Extracellular matrix molecules and synaptic plasticity. Nat Rev Neurosci. 2003;4(6):456–468.
  6. Huntley GW. Synaptic circuit remodelling by matrix metalloproteinases in health and disease. Nat Rev Neurosci. 2012;13(11):743–757.
  7. Allen NJ, Bennett ML, Foo LC, et al. Astrocyte glypicans 4 and 6 promote formation of excitatory synapses via GluA1 AMPA receptors. Nature. 2012;486(7403):410–414.
  8. Dityatev A. Polysialylated neural cell adhesion molecule promotes remodeling and formation of hippocampal synapses. J Neurosci. 2004;24(42):9372–9382.
  9. Albiñana E, Gutierrez-Luengo J, Hernández-Juarez N, et al. Chondroitin sulfate induces depression of synaptic transmission and modulation of neuronal plasticity in rat hippocampal slices. Neural Plast. 2015;2015:463854.
  10. Evers MR, Salmen B, Bukalo O, et al. Impairment of L-type Ca2 channel-dependent forms of hippocampal synaptic plasticity in mice deficient in the extracellular matrix glycoprotein tenascin-C. J Neurosci. 2002;22(16):7117–7194.
  11. Wang D, Ichiyama RM, Zhao R, Andrews MR, Fawcett JW. Chondroitinase combined with rehabilitation promotes recovery of forelimb function in rats with chronic spinal cord injury. J Neurosci. 2011;31(25):9332–9344.
  12. Al-Muhtasib N, Forcelli PA, Conant KE, Vicini S. MMP-1 overexpression selectively alters inhibition in D1 spiny projection neurons in the mouse nucleus accumbens core. Sci Rep. 2018;8(1):16230.
  13. Wiera G, Nowak D, van Hove I, Dziegiel P, Moons L, Mozrzymas JW. Mechanisms of NMDA receptor- and voltage-gated L-type calcium channel-dependent hippocampal LTP critically rely on proteolysis that is mediated by distinct metalloproteinases. J Neurosci. 2017;37(5):1240–1256.
  14. Brzdak P, Nowak D, Wiera G, Mozrzymas JW. Multifaceted roles of metzincins in CNS physiology and pathology: From synaptic plasticity and cognition to neurodegenerative disorders. Front Cell Neurosci. 2017;11:1–22.
  15. Dubey D, McRae PA, Rankin-Gee EK, et al. Increased metalloproteinase activity in the hippocampus following status epilepticus. Epilepsy Res. 2017;132:50–58.
  16. Nagase H, Visse R, Murphy G. Structure and function of matrix metalloproteinases and TIMPs. Cardiovasc Res. 2006;69(3):562–573.
  17. Si-Tayeb K, Monvoisin A, Mazzocco C, et al. Matrix metalloproteinase 3 is present in the cell nucleus and is involved in apoptosis. Am J Pathol. 2006;169(4):1390–1401.
  18. Dandachi NG, Shapiro SD. A protean protease: MMP-12 fights viruses as a protease and a transcription factor. Nat Med. 2014;20(5):470–472.
  19. Nagy V. Matrix metalloproteinase-9 is required for hippocampal late-phase long-term potentiation and memory. J Neurosci. 2006;26(7):1923–1934.
  20. Brzdąk P, Włodarczyk J, Mozrzymas JW, Wójtowicz T. Matrix metalloprotease 3 activity supports hippocampal EPSP-to-Spike plasticity following patterned neuronal activity via the regulation of NMDAR function and calcium flux. Mol Neurobiol. 2017;54(1):804–816.
  21. Magnowska M, Gorkiewicz T, Suska A, et al. Transient ECM protease activity promotes synaptic plasticity. Sci Rep. 2016;6:27757.
  22. Valente MM, Allen M, Bortolotto V, Lim ST, Conant K, Grilli M. The MMP-1/PAR-1 axis enhances proliferation and neuronal differentiation of adult hippocampal neural progenitor cells. Neural Plast. 2015;2015:646595.
  23. Endo K, Takino T, Miyamori H, et al. Cleavage of syndecan-1 by membrane type matrix metalloproteinase-1 stimulates cell migration. J Biol Chem. 2003;278(42):40764–40770.
  24. Marchant DJ, Bellac CL, Moraes TJ, et al. A new transcriptional role for matrix metalloproteinase-12 in antiviral immunity. Nat Med. 2014;20(5):493–502.
  25. Choi DH, Kim E-M, Son HJ, et al. A novel intracellular role of matrix metalloproteinase-3 during apoptosis of dopaminergic cells. J Neurochem. 2008;106(1):405–415.
  26. Biswas MHU, Almeida S, Lopez-Gonzalez R, et al. MMP-9 and MMP-2 contribute to neuronal cell death in iPSC models of frontotemporal dementia with MAPT mutations. Stem Cell Rep. 2016;7(3):316–324.
  27. Jackson HW, Defamie V, Waterhouse P, Khokha R. TIMPs: Versatile extracellular regulators in cancer. Nat Rev Cancer. 2017;17(1):38–53.
  28. Nagase H, Enghild JJ, Suzuki K, Salvesen G. Stepwise activation mechanisms of the precursor of matrix metalloproteinase 3 (stromelysin) by proteinases and (4-aminophenyl)mercuric acetate. Biochemistry. 1990;29(24):5783–5789.
  29. Nagase H, Fields CG, Fields GB. Design and characterization of a fluorogenic substrate selectively hydrolyzed by stromelysin 1 (matrix metalloproteinase-3). J Biol Chem. 1994;269(33):20952–20957.
  30. Traub LM. Tickets to ride: Selecting cargo for clathrin-regulated internalization. Nat Rev Mol Cell Biol. 2009;10(9):583–596.
  31. Eguchi T, Kubota S, Kawata K, et al. Novel transcription factor-like function of human matrix metalloproteinase 3 regulating the CTGF/CCN2 gene. Mol Cell Biol. 2008;28(7):2391–2413.
  32. Choi D-H, Kim J-H, Seo J-H, Lee J, Choi WS, Kim Y-S. Matrix metalloproteinase-3 causes dopaminergic neuronal death through nox1-regenerated oxidative stress. PLoS One. 2014;9(12):e115954.
  33. Vaillant C, Didier-Bazès M, Hutter A, Belin M-F, Thomasset N. Spatiotemporal expression patterns of metalloproteinases and their inhibitors in the postnatal developing rat cerebellum. J Neurosci. 1999;19(12):4994–5004.
  34. Van Hove I, Verslegers M, Buyens T, et al. An aberrant cerebellar development in mice lacking matrix metalloproteinase-3. Mol Neurobiol. 2012;45(1):17–29.
  35. Aerts J, Nys J, Moons L, Hu T-T, Arckens L. Altered neuronal architecture and plasticity in the visual cortex of adult MMP-3-deficient mice. Brain Struct Funct. 2015;220(5):2675–2689.
  36. Nowak D, De Groef L, Moons L, Mozrzymas JW. MMP-3 deficiency does not influence the length and number of CA1 dendrites of hippocampus of adult mice. Acta Neurobiol Exp (Wars). 2018;78(3):281–286.
  37. Wiera G, Wozniak G, Bajor M, Kaczmarek L, Mozrzymas JW. Maintenance of long-term potentiation in hippocampal mossy fiber-CA3 pathway requires fine-tuned MMP-9 proteolytic activity. Hippo­campus. 2013;23(6):529–543.
  38. Imai K, Kusakabe M, Sakakura T, Nakanishi I, Okada Y. Susceptibility of tenascin to degradation by matrix metalloproteinases and serine proteinases. FEBS Lett. 1994;352(2):216–218.
  39. Kochlamazashvili G, Henneberger C, Bukalo O, et al. The extracellular matrix molecule hyaluronic acid regulates hippocampal synaptic plasticity by modulating postsynaptic L-type Ca2+channels. Neuron. 2010;67(1):116–128.
  40. Pauly T, Ratliff M, Pietrowski E, et al. Activity-dependent shedding of the NMDA receptor glycine binding site by matrix metalloproteinase 3: A putative mechanism of postsynaptic plasticity. PLoS One. 2008;3:e2681.
  41. Brzdak P, Włodarczyk J, Mozrzymas JW, Wójtowicz T. Matrix metalloprotease 3 activity supports hippocampal EPSP-to-spike plasticity following patterned neuronal activity via the regulation of NMDAR function and calcium flux. Mol Neurobiol. 2017;54(1):804–816.
  42. Brzdak P, Wójcicka O, Zareba-Koziol M, et al. Synaptic potentiation at basal and apical dendrites of hippocampal pyramidal neurons involves activation of a distinct set of extracellular and intracellular molecular cues. Cereb Cortex. 2019;29(1):283–304.
  43. Meighan SE, Meighan PC, Choudhury P, et al. Effects of extracellular matrix-degrading proteases matrix metalloproteinases 3 and 9 on spatial learning and synaptic plasticity. J Neurochem. 2006;96:1227–1241.
  44. Gonthier B, Nasarre C, Roth L, et al. Functional interaction between matrix metalloproteinase-3 and semaphorin-3C during cortical axonal growth and guidance. Cereb Cortex. 2007;17:1712–1721.
  45. Cua RC, Lau LW, Keough MB, Midha R, Apte SS, Yong VW. Overcoming neurite-inhibitory chondroitin sulfate proteoglycans in the astrocyte matrix. Glia. 2013;61:972–984.
  46. Pizzi MA, Crowe MJ. Transplantation of fibroblasts that overexpress matrix metalloproteinase-3 into the site of spinal cord injury in rats. J Neurotrauma. 2006;23:1750–1765.
  47. Hoyos HC, Marder M, Ulrich R, et al. The role of galectin-3: From oligodendroglial differentiation and myelination to demyelination and remyelination processes in a cuprizone-induced demyelination model. Adv Exp Med Biol. 2016;949:311–332.
  48. McClain JA, Phillips LL, Fillmore HL. Increased MMP-3 and CTGF expression during lipopolysaccharide-induced dopaminergic neuro­degeneration. Neurosci Lett. 2009;460(1):27–31.
  49. Kim YS, Choi DH, Block ML, et al. A pivotal role of matrix metalloproteinase-3 activity in dopaminergic neuronal degeneration via microglial activation. FASEB J. 2007;21(1):179–187.
  50. Choi DH, Kim EM, Son HJ, et al. A novel intracellular role of matrix metalloproteinase-3 during apoptosis of dopaminergic cells. J Neurochem. 2008;106(1):405–415.
  51. Kim EM, Hwang O. Role of matrix metalloproteinase-3 in neurodegeneration. J Neurochem. 2011;116(1):22–32.
  52. Kortekaas R, Leenders KL, van Oostrom JC, et al. Blood-brain barrier dysfunction in parkinsonian midbrain in vivo. Ann Neurol. 2005;57(2):176–179.
  53. Choi DH, Kim YJ, Kim YG, Joh TH, Beal MF, Kim YS. Role of matrix metalloproteinase 3-mediated alpha-synuclein cleavage in dopaminergic cell death. J Biol Chem. 2011;286(16):14168–14177.
  54. Yoshiyama Y, Asahina M, Hattori T. Selective distribution of matrix metalloproteinase-3 (MMP-3) in Alzheimer’s disease brain. Acta ­Neuropathol. 2000;99(2):91–95.
  55. Deb S, Gottschall PE. Increased production of matrix metalloproteinases in enriched astrocyte and mixed hippocampal cultures treated with beta-amyloid peptides. J Neurochem. 1996;66(4):1641–1647.
  56. Baig S, Kehoe PG, Love S. MMP-2, -3 and -9 levels and activity are not related to Abeta load in the frontal cortex in Alzheimer’s disease. Neuropathol Appl Neurobiol. 2008;34(2):205–215.
  57. Reitz C, van Rooij FJ, de Maat MP, et al. Matrix metalloproteinase 3 haplotypes and dementia and Alzheimer’s disease. The Rotterdam Study. Neurobiol Aging. 2008;29(6):874–881.
  58. Mlekusch R, Humpel C. Matrix metalloproteinases-2 and -3 are reduced in cerebrospinal fluid with low beta-amyloid1-42 levels. Neurosci Lett. 2009;466(3):135–138.
  59. Stomrud E, Björkqvist M, Janciauskiene S, Minthon L, Hansson O. Alterations of matrix metalloproteinases in the healthy elderly with increased risk of prodromal Alzheimer’s disease. Alzheimers Res Ther. 2010;2(3):20–20.
  60. Peng M, Jia J, Qin W. Plasma gelsolin and matrix metalloproteinase 3 as potential biomarkers for Alzheimer disease. Neurosci Lett. 2015;595:116–121.
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