Search Advanced

AIMS Molecular Science

2017, Volume 4, Issue 4: 446-462. doi: 10.3934/molsci.2017.4.446
Previous Article Next Article
Review

Calpain inhibition as a possible new therapeutic target in multiple sclerosis

  • 1.
    Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA
  • 2.
    Department of Pathology, Microbiology and Immunology, University of South Carolina, Columbia, SC, USA
  • 3.
    Department of Neurosurgery, Medical University of South Carolina, Charleston, SC, USA
  • 4.
    Department of Ophthalmology, Medical University of South Carolina, Charleston, SC, USA
  • 5.
    Research Service, Ralph H. Johnson VA Medical Center, Charleston, SC, USA
  • Received: 04 May 2017 Accepted: 19 October 2017 Published: 26 October 2017

  • Multiple sclerosis (MS), the most common chronic autoimmune inflammatory disease of the central nervous system (CNS), is characterized by demyelination and neurodegeneration. In particular, neurodegeneration is a major factor in disease progression with neuronal death and irreversible axonal damage leading to disability. MS is manageable with current therapies that are directed towards immunomodulation but there are no available therapies for neuroprotection. The complex pathophysiology and heterogeneity of MS indicate that therapeutic agents should be directed to both the inflammatory and neurodegenerative arms of the disease. Activity of the Ca2+ activated protease calpain has been previously implicated in progression of MS and its primary animal model, experimental autoimmune encephalomyelitis (EAE). The effects of calpain inhibitors in EAE involve downregulation of Th1/Th17 inflammatory responses and promotion of regulatory T cells, overall leading to decreased inflammatory cell infiltration in CNS tissues. Furthermore, analysis of brains, spinal cords and optic nerves from EAE animals revealed decreases in axon degeneration, motor neuron and retinal ganglion cell death. This resulted in improved severity of paralysis and preservation of visual function. Taken together, the studies presented in this brief review suggest that use of calpain inhibitors in combination with an immunomodulatory agent may be a potential therapeutic strategy for MS and optic neuritis.

    Citation: Amena W. Smith, Swapan K. Ray, Arabinda Das, Kenkichi Nozaki, Baerbel Rohrer, Naren L. Banik. Calpain inhibition as a possible new therapeutic target in multiple sclerosis[J]. AIMS Molecular Science, 2017, 4(4): 446-462. doi: 10.3934/molsci.2017.4.446

    Related Papers:

  • Multiple sclerosis (MS), the most common chronic autoimmune inflammatory disease of the central nervous system (CNS), is characterized by demyelination and neurodegeneration. In particular, neurodegeneration is a major factor in disease progression with neuronal death and irreversible axonal damage leading to disability. MS is manageable with current therapies that are directed towards immunomodulation but there are no available therapies for neuroprotection. The complex pathophysiology and heterogeneity of MS indicate that therapeutic agents should be directed to both the inflammatory and neurodegenerative arms of the disease. Activity of the Ca2+ activated protease calpain has been previously implicated in progression of MS and its primary animal model, experimental autoimmune encephalomyelitis (EAE). The effects of calpain inhibitors in EAE involve downregulation of Th1/Th17 inflammatory responses and promotion of regulatory T cells, overall leading to decreased inflammatory cell infiltration in CNS tissues. Furthermore, analysis of brains, spinal cords and optic nerves from EAE animals revealed decreases in axon degeneration, motor neuron and retinal ganglion cell death. This resulted in improved severity of paralysis and preservation of visual function. Taken together, the studies presented in this brief review suggest that use of calpain inhibitors in combination with an immunomodulatory agent may be a potential therapeutic strategy for MS and optic neuritis.


    加载中
    [1] Dargahi N, Katsara M, Tselios T, et al. (2017) Multiple Sclerosis: Immunopathology and Treatment Update. Brain Sci 7: 78. doi: 10.3390/brainsci7070078
    [2] Confavreux C, Vukusic S (2014) The clinical course of multiple sclerosis. Handb Clin Neurol 122: 343-369. doi: 10.1016/B978-0-444-52001-2.00014-5
    [3] Confavreux C, Vukusic S, Moreau T, et al. (2001) Relapses and progression of disability in multiple sclerosis. N Engl J Med 343: 1430-1438.
    [4] Kinzel S, Weber MS (2016) B Cell-Directed Therapeutics in Multiple Sclerosis: Rationale and Clinical Evidence. Cns Drug 30: 1137-1148. doi: 10.1007/s40263-016-0396-6
    [5] Fernando NT, Koch M, Rothrock C, et al. (2008) Tumor escape from endogenous, extracellular matrix-associated angiogenesis inhibitors by up-regulation of multiple proangiogenic factors. Clin Cancer Res 14: 1529-1539. doi: 10.1158/1078-0432.CCR-07-4126
    [6] Rottlaender A, Kuerten S. (2015) Stepchild or Prodigy? Neuroprotection in Multiple Sclerosis (MS) Research. Int J Mol Sci 16: 14850-14865.
    [7] Popescu V, Agosta F, Hulst HE, et al. (2013) Brain atrophy and lesion load predict long term disability in multiple sclerosis. J Neurol Neurosur Psychiatr 84: 1082-1091. doi: 10.1136/jnnp-2012-304094
    [8] Vickers JC, King AE, Woodhouse A, et al. (2009) Axonopathy and cytoskeletal disruption in degenerative diseases of the central nervous system. Brain Res Bull 80: 217-223. doi: 10.1016/j.brainresbull.2009.08.004
    [9] Mentis AA, Dardiotis E, Grigoriadis N, et al. (2017) Viruses and Multiple Sclerosis: From Mechanisms and Pathways to Translational Research Opportunities. Mol neurobiol 54: 3911-3923. doi: 10.1007/s12035-017-0530-6
    [10] Berer K, Krishnamoorthy G (2014) Microbial view of central nervous system autoimmunity. FEBS lett 588: 4207-4213. doi: 10.1016/j.febslet.2014.04.007
    [11] Geginat J, Paroni M, Pagani M, et al. (2017) The Enigmatic Role of Viruses in Multiple Sclerosis: Molecular Mimicry or Disturbed Immune Surveillance? Trend in Immunol 38: 498-512. doi: 10.1016/j.it.2017.04.006
    [12] Brownlee WJ, Miller DH (2014) Clinically isolated syndromes and the relationship to multiple sclerosis. J Clin Neurosci 21: 2065-2071. doi: 10.1016/j.jocn.2014.02.026
    [13] Rocca MA, Preziosa P, Mesaros S, et al. (2016) Clinically Isolated Syndrome Suggestive of Multiple Sclerosis: Dynamic Patterns of Gray and White Matter Changes-A 2-year MR Imaging Study. Radiology 278: 841-853. doi: 10.1148/radiol.2015150532
    [14] Klaver R, Popescu V, Voorn P, et al. (2015) Neuronal and axonal loss in normal-appearing gray matter and subpial lesions in multiple sclerosis. J Neuropathol Exp Neurol 74: 453-458. doi: 10.1097/NEN.0000000000000189
    [15] De SN, Giorgio A, Battaglini M, et al. (2010) Assessing brain atrophy rates in a large population of untreated multiple sclerosis subtypes. Neurology 74: 1868-1876. doi: 10.1212/WNL.0b013e3181e24136
    [16] Alonso A, Hernán MA (2008) Temporal trends in the incidence of multiple sclerosis: a systematic review. Neurology 71: 129-135. doi: 10.1212/01.wnl.0000316802.35974.34
    [17] Rojas JI, Patrucco L, Miguez J, et al. (2016) Brain atrophy in multiple sclerosis: therapeutic, cognitive and clinical impact. Arq Neuro-Psiquiat 74: 235-243. doi: 10.1590/0004-282X20160015
    [18] Rojas JI, Patrucco L, Besada C, et al. (2010) [Brain atrophy in clinically isolated syndrome]. Neurología 25: 430-434.
    [19] Tawse KL, Gobuty M, Mendoza-Santiesteban C (2014) Optical coherence tomography shows retinal abnormalities associated with optic nerve disease. Br J Ophthalmol 98: ii30-3. doi: 10.1136/bjophthalmol-2013-304301
    [20] You Y, Gupta VK, Li JC, et al. (2013) Optic neuropathies: characteristic features and mechanisms of retinal ganglion cell loss. Rev Neurosci 24: 301-321.
    [21] Namekata K, Kimura A, Kawamura K, et al. (2013) Dock3 attenuates neural cell death due to NMDA neurotoxicity and oxidative stress in a mouse model of normal tension glaucoma. Cell Death Diff 20: 1250-1256. doi: 10.1038/cdd.2013.91
    [22] Burkholder BM, Osborne B, Loguidice MJ, et al. (2009) Macular volume determined by optical coherence tomography as a measure of neuronal loss in multiple sclerosis. Arch Neurol 66: 1366.
    [23] Frohman EM, Dwyer MG, Frohman T, et al. (2009) Relationship of optic nerve and brain conventional and non-conventional MRI measures and retinal nerve fiber layer thickness, as assessed by OCT and GDx: a pilot study. J Neurol Sci 282: 96-105. doi: 10.1016/j.jns.2009.04.010
    [24] Pineles SL, Birch EE, Talman LS, et al. (2011) One eye or two: a comparison of binocular and monocular low-contrast acuity testing in multiple sclerosis. Am J Ophthalmol 152: 133-140. doi: 10.1016/j.ajo.2011.01.023
    [25] Martin R, Mcfarland HF, Mcfarlin DE (1992) Immunological aspects of demyelinating diseases. Annu Rev Immunol 10: 153. doi: 10.1146/annurev.iy.10.040192.001101
    [26] Hobom M, Storch MK, Weissert R, et al. (2004) Mechanisms and time course of neuronal degeneration in experimental autoimmune encephalomyelitis. Brain Pathol 14: 148-157. doi: 10.1111/j.1750-3639.2004.tb00047.x
    [27] Croxford AL, Kurschus FC, Waisman A (2011) Mouse models for multiple sclerosis: historical facts and future implications. Biochim Biophys Acta 1812: 177-183. doi: 10.1016/j.bbadis.2010.06.010
    [28] Shields DC, Banik NL (1999) Pathophysiological role of calpain in experimental demyelination. J Neurosci Res 55: 533-541. doi: 10.1002/(SICI)1097-4547(19990301)55:5<533::AID-JNR1>3.0.CO;2-8
    [29] Hassen GW, Feliberti J, Kesner L, et al. (2006) A novel calpain inhibitor for the treatment of acute experimental autoimmune encephalomyelitis. J Neuroimmunol 180: 135-146. doi: 10.1016/j.jneuroim.2006.08.005
    [30] Guyton MK, Das A, Samantaray S, et al. (2010) Calpeptin attenuated inflammation, cell death, and axonal damage in animal model of multiple sclerosis. J Neurosci Res 88: 2398-2408.
    [31] Kobeissy FH. (2015) Brain Neurotrauma: Molecular, Neuropsychological, and Rehabilitation Aspects. Crc Press.
    [32] Sun JF, Yang HL, Huang YH, et al. (2017) CaSR and calpain contribute to the ischemia reperfusion injury of spinal cord. Neurosci lett 646: 49-55. doi: 10.1016/j.neulet.2017.03.009
    [33] Samantaray S, Knaryan VH, Shields DC, et al. (2013) Critical role of calpain in spinal cord degeneration in Parkinson's disease. J Neurochem 127: 880. doi: 10.1111/jnc.12374
    [34] Siklos M, Benaissa M, Thatcher GRJ (2015) Cysteine proteases as therapeutic targets: does selectivity matter? A systematic review of calpain and cathepsin inhibitors. Acta pharmaceutica Sinica B 5: 506-519.
    [35] Smith AW, Rohrer B, Wheless L, et al. (2016) Calpain inhibition reduces structural and functional impairment of retinal ganglion cells in experimental optic neuritis. J Neurochem 139: 270-284. doi: 10.1111/jnc.13770
    [36] Ono Y, Sorimachi H (2012) Calpains: an elaborate proteolytic system. Biochim Biophys Acta 1824: 224-236. doi: 10.1016/j.bbapap.2011.08.005
    [37] Pietrobon D, Di VF, Pozzan T (1990) Structural and functional aspects of calcium homeostasis in eukaryotic cells. Eur J Biochem 193: 599-622. doi: 10.1111/j.1432-1033.1990.tb19378.x
    [38] Wu HY, Tomizawa K, Matsui H (2007) Calpain-calcineurin signaling in the pathogenesis of calcium-dependent disorder. Acta Medica Okayama 61: 123-137.
    [39] Diaz-Sanchez M, Williams K, Deluca GC, et al. (2006) Protein co-expression with axonal injury in multiple sclerosis plaques. Acta Neuropathol 111: 289. doi: 10.1007/s00401-006-0045-0
    [40] Yan F, Sun W, Shi Y, et al. (2009) Glutamate excitotoxicity inflicts paranodal myelin splitting and retraction. Plos One 4: e6705. doi: 10.1371/journal.pone.0006705
    [41] Banik NL, Chou CH, Deibler GE, et al. (1994) Peptide bond specificity of calpain: proteolysis of human myelin basic protein. J Neurosci Res 37: 489-496. doi: 10.1002/jnr.490370408
    [42] Howe CL, Lafrancecorey RG, Mirchia K, et al. (2016) Neuroprotection mediated by inhibition of calpain during acute viral encephalitis. Sci Rep 6: 28699. doi: 10.1038/srep28699
    [43] Machado VM, Morte MI, Carreira BP, et al. (2015) Involvement of calpains in adult neurogenesis: implications for stroke. Front Cell Neurosci 9: 22.
    [44] Knaryan VH, Samantaray S, Park S, et al. (2014) SNJ-1945, a calpain inhibitor, protects SH-SY5Y cells against MPP(+) and rotenone. J Neurochem 130: 280-290. doi: 10.1111/jnc.12629
    [45] Donkor IO (2000) A survey of calpain inhibitors. Curr Med Chem 7: 1171-1181. doi: 10.2174/0929867003374129
    [46] Shirasaki Y, Miyashita H, Yamaguchi M, et al. (2005) Exploration of orally available calpain inhibitors: peptidyl alpha-ketoamides containing an amphiphile at P3 site. Bioorg Med Chem 13: 4473-4484. doi: 10.1016/j.bmc.2005.04.059
    [47] Donkor IO, Zheng X, Miller DD (2000) Synthesis and calpain inhibitory activity of alpha-ketoamides with 2,3-methanoleucine stereoisomers at the P2 position. Bioorg Med Chem Lett 10: 2497-2500. doi: 10.1016/S0960-894X(00)00518-7
    [48] Carragher NO (2006) Calpain inhibition: a therapeutic strategy targeting multiple disease states. Curr Pharm Design 12: 615-638. doi: 10.2174/138161206775474314
    [49] Barrett AJ, Kembhavi AA, Brown MA, et al. (1982) L-trans-Epoxysuccinyl-leucylamido (4-guanidino) butane (E-64) and its analogues as inhibitors of cysteine proteinases including cathepsins B, H and L. Biochem J 201: 189-198. doi: 10.1042/bj2010189
    [50] Saido TC, Sorimachi H, Suzuki K (1994) Calpain: new perspectives in molecular diversity and physiological-pathological involvement. FASEB J 8: 814-822.
    [51] Podbielska M, Das A, Smith AW, et al. (2016) Neuron-microglia interaction induced bi-directional cytotoxicity associated with calpain activation. J Neurochem 139: 440-455. doi: 10.1111/jnc.13774
    [52] Xiao T, Zhang Y, Wang Y, et al. (2013) Activation of an apoptotic signal transduction pathway involved in the upregulation of calpain and apoptosis-inducing factor in aldosterone-induced primary cultured cardiomyocytes. Food Chem Toxicol 53: 364-370. doi: 10.1016/j.fct.2012.12.022
    [53] Imai T, Kosuge Y, Endo-Umeda K, et al. (2014) Protective effect of S-allyl-L-cysteine against endoplasmic reticulum stress-induced neuronal death is mediated by inhibition of calpain. Amino Acids 46: 385-393. doi: 10.1007/s00726-013-1628-4
    [54] Li H, Zhang N, Sun G, et al. (2013) Inhibition of the group I mGluRs reduces acute brain damage and improves long-term histological outcomes after photothrombosis-induced ischaemia. ASN Neuro 5: 195.
    [55] Ray SK, Neuberger TJ, Deadwyler G, et al. (2002) Calpain and calpastatin expression in primary oligodendrocyte culture: preferential localization of membrane calpain in cell processes. J Neurosci Res 70: 561-569. doi: 10.1002/jnr.10414
    [56] Das A, Garner DP, Del Re AM, et al. (2006) Calpeptin provides functional neuroprotection to rat retinal ganglion cells following Ca2+ influx. Brain Res 1084: 146-157. doi: 10.1016/j.brainres.2006.02.051
    [57] Guyton MK, Brahmachari S, Das A, et al. (2009) Inhibition of calpain attenuates encephalitogenicity of MBP-specific T cells. J Neurochem 110: 1895-1907. doi: 10.1111/j.1471-4159.2009.06287.x
    [58] Guyton MK, Das A, Samantaray S, et al. (2010) Calpeptin attenuated inflammation, cell death, and axonal damage in animal model of multiple sclerosis. J Neurosci Res 88: 2398-2408.
    [59] Neffe AT, Abell AD (2005) Developments in the design and synthesis of calpain inhibitors. Curr Opin Drug Discov Develop 8: 684-700.
    [60] Das A, Sribnick EA, Wingrave JM, et al. (2005) Calpain activation in apoptosis of ventral spinal cord 4.1 (VSC4.1) motoneurons exposed to glutamate: calpain inhibition provides functional neuroprotection. J Neurosci Res 81: 551-562.
    [61] Sharma A1 (2007) Sustained elevation of intracellular cGMP causes oxidative stress triggering calpain-mediated apoptosis in photoreceptor degeneration. Curr Eye Res 32: 259-269. doi: 10.1080/02713680601161238
    [62] Min Y, Zhu W, Zheng X, et al. (2016) Effect of glutamate on lysosomal membrane permeabilization in primary cultured cortical neurons. Mol Med Rep 13: 2499-2505. doi: 10.3892/mmr.2016.4819
    [63] Shirasaki Y, Yamaguchi MH (2006) Retinal penetration of calpain inhibitors in rats after oral administration. J Ocul Pharmacol Ther 22: 417-424. doi: 10.1089/jop.2006.22.417
    [64] Koumura A, Nonaka Y, Hyakkoku K, et al. (2008). A novel calpain inhibitor, ((1S)-1((((1S)-1-benzyl-3-cyclopropylamino-2,3-di-oxopropyl)amino)carbonyl)-3-met hylbutyl) carbamic acid 5-methoxy-3-oxapentyl ester, protects neuronal cells from cerebral ischemia-induced damage in mice. Neurosci 157: 309-318. doi: 10.1016/j.neuroscience.2008.09.007
    [65] Nakajima E, Hammond KB, Rosales JL, et al. (2011) Calpain, not caspase, is the causative protease for hypoxic damage in cultured monkey retinal cells. Invest Ophthalmol Vis Sci 52: 7059-7067. doi: 10.1167/iovs.11-7497
    [66] Trager N, Butler JT, Haque A, et al. (2013) The Involvement of Calpain in CD4+ T Helper Cell Bias in Multple Sclerosis. J Clin Cell Iimmunol 4: 1000153.
    [67] Surh YJ, Chun KS, Cha HH, et al. (2001) Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: down-regulation of COX-2 and iNOS through suppression of NF-kappa B activation. Mutat Res s480-481: 243-268.
    [68] Potz BA, Sabe AA, Elmadhun NY, et al. (2017) Calpain inhibition decreases inflammatory protein expression in vessel walls in a model of chronic myocardial ischemia. Surgery 161: 1394-1404. doi: 10.1016/j.surg.2016.11.009
    [69] Butler JT, Samantaray S, Beeson CC, et al. (2009) Involvement of calpain in the process of Jurkat T cell chemotaxis. J Neurosci Res 87: 626-635. doi: 10.1002/jnr.21882
    [70] Mikosik A, Jasiulewicz A, Daca A, et al. (2016) Roles of calpain-calpastatin system (CCS) in human T cell activation. Oncotarget 7: 76479-76495.
    [71] Moretti D, Del BB, Allavena G, et al. (2014) Calpains and cancer: friends or enemies? Arch Biochem Biophys 564: 26-36. doi: 10.1016/j.abb.2014.09.018
    [72] Deshpande RV, Goust JM, Hogan EL, et al. (1995) Calpain secreted by activated human lymphoid cells degrades myelin. J Neurosci Res 42: 259-265. doi: 10.1002/jnr.490420214
    [73] Jantzie LL, Winer JL, Corbett CJ, et al. (2016) Erythropoietin Modulates Cerebral and Serum Degradation Products from Excess Calpain Activation following Prenatal Hypoxia-Ischemia. Dev Neurosci 38: 15-26. doi: 10.1159/000441024
    [74] Guyton MK, Sribnick EA, Ray SK, et al. (2005) A role for calpain in optic neuritis. Ann NY Acad Sci 1053: 48-54. doi: 10.1196/annals.1344.005
    [75] Cerghet M, Skoff RP, Bessert D, et al (2006) Proliferation and death of oligodendrocytes and myelin proteins are differentially regulated in male and female rodents. J Neurosci 26: 1439-1447. doi: 10.1523/JNEUROSCI.2219-05.2006
    [76] Ding ZJ, Chen X, Tang XX, et al. (2015) Calpain inhibitor PD150606 attenuates glutamate induced spiral ganglion neuron apoptosis through apoptosis inducing factor pathway in vitro. PLoS One 10: e0123130. doi: 10.1371/journal.pone.0123130
    [77] Das A, Guyton MK, Matzelle DD, et al. (2008) Time-dependent increases in protease activities for neuronal apoptosis in spinal cords of Lewis rats during development of acute experimental autoimmune encephalomyelitis. J Neurosci Res 86: 2992-3001. doi: 10.1002/jnr.21737
    [78] Vosler PS, Brennan CS, Chen J (2008) Calpain-mediated signaling mechanisms in neuronal injury and neurodegeneration. Mol Neurobiol 38: 78-100. doi: 10.1007/s12035-008-8036-x
    [79] Schaecher K, Goust JM, Banik NL (2004) The effects of calpain inhibition on IkB alpha degradation after activation of PBMCs: identification of the calpain cleavage sites. Neurochem Res 29: 1443-1451. doi: 10.1023/B:NERE.0000026410.56000.dd
    [80] Gerondakis S, Grumont R, Rourke I, et al. (1998) The regulation and roles of Rel/NF-kappa B transcription factors during lymphocyte activation. Curr Opin Immunol 10: 353-359. doi: 10.1016/S0952-7915(98)80175-1
    [81] Miyazaki T, Taketomi Y, Saito Y, et al. (2015) Calpastatin counteracts pathological angiogenesis by inhibiting suppressor of cytokine signaling 3 degradation in vascular endothelial cells. Circ Res 116: 1170-1181. doi: 10.1161/CIRCRESAHA.116.305363
    [82] Datta R, Naura AS, Zerfaoui M, et al. (2011) PARP-1 deficiency blocks IL-5 expression through calpain-dependent degradation of STAT-6 in a murine asthma model. Allergy 66: 853-861. doi: 10.1111/j.1398-9995.2011.02549.x
    [83] Tahvanainen J, Kallonen T, Lähteenmäki H, et al. (2009) PRELI is a mitochondrial regulator of human primary T-helper cell apoptosis, STAT6, and Th2-cell differentiation. Blood 113: 1268-1277. doi: 10.1182/blood-2008-07-166553
    [84] Hendry L, John S (2004) Regulation of STAT signalling by proteolytic processing. Eur J Biochem 271: 4613-4620. doi: 10.1111/j.1432-1033.2004.04424.x
    [85] Svensson L, Mcdowall A, Giles K M, et al. (2010) Calpain 2 controls turnover of LFA-1 adhesions on migrating T lymphocytes. PLoS One 5: e15090. doi: 10.1371/journal.pone.0015090
    [86] Stewart MP, Mcdowall A, Hogg N (1998) LFA-1-mediated adhesion is regulated by cytoskeletal restraint and by a Ca2+-dependent protease, calpain. J cell Biol 140: 699-707. doi: 10.1083/jcb.140.3.699
    [87] Soede RD, Driessens MH, Ruulsvan SL, et al. (1999) LFA-1 to LFA-1 signals involve zeta-associated protein-70 (ZAP-70) tyrosine kinase: relevance for invasion and migration of a T cell hybridoma. J Immunol 163: 4253-4261.
    [88] Engelhard VH, Altrich-Vanlith M, Ostankovitch M, et al. (2006) Post-translational modifications of naturally processed MHC-binding epitopes. Curr Opin Immunol 18: 92-97. doi: 10.1016/j.coi.2005.11.015
    [89] Imam SA, Guyton MK, Haque A, et al. (2007) Increased calpain correlates with Th1 cytokine profile in PBMCs from MS patients. J Neuroimmunol 190: 139-145. doi: 10.1016/j.jneuroim.2007.07.016
    [90] Zhang Z, Huang Z, Dai H, et al. (2015) Therapeutic Efficacy of E-64-d, a Selective Calpain Inhibitor, in Experimental Acute Spinal Cord Injury. BioMed Res Int: 134242.
    [91] Posmantur R, Hayes RL, Dixon CE, et al. (1994) Neurofilament 68 and neurofilament 200 protein levels decrease after traumatic brain injury. J Neurotrauma 11: 533-545. doi: 10.1089/neu.1994.11.533
    [92] Zhang JN, Michel U, Lenz C, et al. (2016) Calpain-mediated cleavage of collapsin response mediator protein-2 drives acute axonal degeneration. Sci Rep 6: 37050. doi: 10.1038/srep37050
    [93] Wilson GN, Smith MA, Inman DM, et al. (2016) Early Cytoskeletal Protein Modifications Precede Overt Structural Degeneration in the DBA/2J Mouse Model of Glaucoma. Front Neurosci 10: 494.
    [94] Saito K, Elce JS, Hamos E, et al. (1993) Widespread activation of calcium-activated neutral proteinase (calpain) in the brain in Alzheimer disease: a potential molecular basis for neuronal degeneration. Proc Natl Acad Sci USA 90: 2628-2632. doi: 10.1073/pnas.90.7.2628
    [95] Dowling P, Husar W, Menonna J, et al. (1997) Cell death and birth in multiple sclerosis brain. J Neurol Sci 149: 1-11. doi: 10.1016/S0022-510X(97)05213-1
    [96] Gerónimoolvera C, Montiel T, Rinconheredia R, et al. (2017) Autophagy fails to prevent glucose deprivation/glucose reintroduction-induced neuronal death due to calpain-mediated lysosomal dysfunction in cortical neurons. Cell Death Disease 8: e2911. doi: 10.1038/cddis.2017.299
    [97] Sharma AK, Rohrer B (2017) Calcium-induced calpain mediates apoptosis via caspase-3 in a mouse photoreceptor cell line. J Biol Chem 292: 13186. doi: 10.1074/jbc.A117.401037
    [98] Pitt D, Werner P, Raine CS (2000) Glutamate excitotoxicity in a model of multiple sclerosis. Nat Med 6: 67-70. doi: 10.1038/71555
    [99] Shields DC, Banik NL (1999) A putative mechanism of demyelination in multiple sclerosis by a proteolytic enzyme, calpain. Proc Natl Acad Sci USA 96: 11486-11491. doi: 10.1073/pnas.96.20.11486
    [100] Zhang ZW, Qin XY, Che FY, et al. (2015) Effects of beta 2 adrenergic agonists on axonal injury and mitochondrial metabolism in experimental autoimmune encephalomyelitis rats. Genetics and molecular research: GMR 14: 13572-13581. doi: 10.4238/2015.October.28.17
    [101] Kivisäkk P, Mahad DJ, Callahan MK, et al. (2003) Human cerebrospinal fluid central memory CD4+ T cells: evidence for trafficking through choroid plexus and meninges via P-selectin. Proc Natl Acad Sci USA 100: 8389-8394. doi: 10.1073/pnas.1433000100
    [102] Lassmann H, Ransohoff RM (2004) The CD4-Th1 model for multiple sclerosis: a critical [correction of crucial] re-appraisal. Trends Immunol 25: 132-137. doi: 10.1016/j.it.2004.01.007
    [103] Dhib S (2003) Glatiramer acetate-reactive peripheral blood mononuclear cells respond to multiple myelin antigens with a Th2-biased phenotype. J Neuroimmunol 140: 163-171. doi: 10.1016/S0165-5728(03)00170-X
    [104] Issazadeh S, Mustafa M, Ljungdahl A, et al. (1995) Interferon gamma, interleukin 4 and transforming growth factor beta in experimental autoimmune encephalomyelitis in Lewis rats: dynamics of cellular mRNA expression in the central nervous system and lymphoid cells. J Neurosci Res 40: 579-590. doi: 10.1002/jnr.490400503
    [105] Kennedy MK, Torrance DS, Picha KS, et al. (1992) Analysis of cytokine mRNA expression in the central nervous system of mice with experimental autoimmune encephalomyelitis reveals that IL-10 mRNA expression correlates with recovery. J Immunol 149: 2496.
    [106] Nishihara M, Ogura H, Ueda N, et al. (2007) IL-6-gp130-STAT3 in T cells directs the development of IL-17+ Th with a minimum effect on that of Treg in the steady state. Int Immunol 19: 695-702. doi: 10.1093/intimm/dxm045
    [107] Immunology N (2005) Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol 6: 1123-1132. doi: 10.1038/ni1254
    [108] Park H, Li Z, Yang XO, et al. (2005) A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol 6: 1133-1141. doi: 10.1038/ni1261
    [109] Passos GRD, Sato DK, Becker J, et al. (2016) Th17 Cells Pathways in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders: Pathophysiological and Therapeutic Implications. Mediat Inflamm 2016: 1-11.
    [110] Zahra S, Rozita D, Masoumeh B, et al. (2016) Differential Frequency of CD8+ T Cell Subsets in Multiple Sclerosis Patients with Various Clinical Patterns. PLoS One 11: e0159565. doi: 10.1371/journal.pone.0159565
    [111] Kebir H, Ifergan I, Alvarez JI, et al. (2009) Preferential recruitment of interferon-gamma-expressing TH17 cells in multiple sclerosis. Ann Neurol 66: 390-402. doi: 10.1002/ana.21748
    [112] Thackray SJ, Mowat CG, Chapman SK (2008) Exploring the mechanism of tryptophan 2,3-dioxygenase. Biochem Soc Trans 36: 1120-1123. doi: 10.1042/BST0361120
    [113] Stone TW, Darlington LG (2002) Endogenous kynurenines as targets for drug discovery and development. Nat Rev 1: 609-620.
    [114] Munn DH, Mellor AL (2007) Indoleamine 2,3-dioxygenase and tumor-induced tolerance. J Clin Invest 117: 1147-1154. doi: 10.1172/JCI31178
    [115] Fallarino F, Grohmann U, You S, et al. (2006) The combined effects of tryptophan starvation and tryptophan catabolites down-regulate T cell receptor zeta-chain and induce a regulatory phenotype in naive T cells. J Immunol 176: 6752-6761. doi: 10.4049/jimmunol.176.11.6752
    [116] Mackenzie CR, Heseler K, Müller A, et al. (2007) Role of indoleamine 2,3-dioxygenase in antimicrobial defence and immuno-regulation: tryptophan depletion versus production of toxic kynurenines. Curr Drug Metab 8: 237-244. doi: 10.2174/138920007780362518
    [117] Mancuso R, Hernis A, Agostini S, et al. (2015) Indoleamine 2,3 Dioxygenase (IDO) Expression and Activity in Relapsing-Remitting Multiple Sclerosis. Plos One 10: e0130715. doi: 10.1371/journal.pone.0130715
    [118] Sousa DA, Porto WF, Silva MZ, et al. (2016) Influence of Cysteine and Tryptophan Substitution on DNA-Binding Activity on Maize α-Hairpinin Antimicrobial Peptide. Molecules 21: 1062. doi: 10.3390/molecules21081062
    [119] Smith AW, Doonan BP, Tyor WR, et al. (2011) Regulation of Th1/Th17 cytokines and IDO gene expression by inhibition of calpain in PBMCs from MS patients. J Neuroimmunol 232: 179-185. doi: 10.1016/j.jneuroim.2010.09.030
    [120] Cilingir V, Batur M, Bulut MD, et al. (2017) The association between retinal nerve fibre layer thickness and corpus callosum index in different clinical subtypes of multiple sclerosis. Neurol Sci 38: 1223-1232. doi: 10.1007/s10072-017-2947-0
    [121] Britze J, Pihljensen G, Frederiksen JL (2017) Retinal ganglion cell analysis in multiple sclerosis and optic neuritis: a systematic review and meta-analysis. J Neurol 264: 1837-1853. doi: 10.1007/s00415-017-8531-y
    [122] Mowry EM, Loguidice MJ, Daniels AB, et al. (2009) Vision related quality of life in multiple sclerosis: correlation with new measures of low and high contrast letter acuity. J Neurol Neurosurg Psychia 80: 767-772. doi: 10.1136/jnnp.2008.165449
    [123] Mackay DD (2015) Should patients with optic neuritis be treated with steroids? Curr Opin Ophthalmol 26: 439-444. doi: 10.1097/ICU.0000000000000197
    [124] Dimitriu C, Bach M, Lagrèze WA, et al. (2008) Methylprednisolone fails to preserve retinal ganglion cells and visual function after ocular ischemia in rats. Invest Ophthalmol Vis Sci 49: 5003-5007. doi: 10.1167/iovs.08-1869
    [125] Das A, Guyton MK, Smith A, et al. (2013) Calpain inhibitor attenuated optic nerve damage in acute optic neuritis in rats. J Neurochem 124: 133-143. doi: 10.1111/jnc.12064
    [126] Shields DC, Tyor WR, Deibler GE, et al. (1998) Increased calpain expression in experimental demyelinating optic neuritis: an immunocytochemical study. Brain Res 784: 299-304. doi: 10.1016/S0006-8993(97)01381-4
    [127] Hoffmann DB, Williams SK, Jovana B, et al. (2013) Calcium influx and calpain activation mediate preclinical retinal neurodegeneration in autoimmune optic neuritis. J Neuropathol Exp Neurol 72: 745-757. doi: 10.1097/NEN.0b013e31829c7370
    [128] Shimazawa M, Suemori S, Inokuchi Y, et al. (2010) A novel calpain inhibitor, ((1S)-1-((((1S)-1-Benzyl-3-cyclopropylamino-2,3-di-oxopropyl)amino)carbonyl)-3-methylbutyl)carbamic acid 5-methoxy-3-oxapentyl ester (SNJ-1945), reduces murine retinal cell death in vitro and in vivo. J Pharm Exp Ther 332: 380-387. doi: 10.1124/jpet.109.156612
    [129] Imai S, Shimazawa M, Nakanishi T, et al. (2010) Calpain inhibitor protects cells against light-induced retinal degeneration. J Pharm Exp Ther 335: 645-652. doi: 10.1124/jpet.110.171298
    [130] Yokoyama Y, Maruyama K, Yamamoto K, et al. (2014) The role of calpain in an in vivo model of oxidative stress-induced retinal ganglion cell damage. Biochem Biophys Res Comm 451: 510-515. doi: 10.1016/j.bbrc.2014.08.009
    [131] Wang Y, Liu Y, Lopez D, et al. (2017) Protection against TBI-induced neuronal death with post-treatment with a selective calpain-2 inhibitor in mice. J Neurotrauma.
    [132] Tsuda S, Tanaka Y, Kunikata H, et al. (2016) Real-time imaging of RGC death with a cell-impermeable nucleic acid dyeing compound after optic nerve crush in a murine model. Exp Eye Res 146: 179-188. doi: 10.1016/j.exer.2016.03.017
    [133] Ryu M, Yasuda M, Shi D, et al. (2012) Critical role of calpain in axonal damage-induced retinal ganglion cell death. J Neurosci Res 90: 802-815. doi: 10.1002/jnr.22800
    [134] Nemeth CL, Drummond GT, Mishra MK, et al. (2017) Uptake of dendrimer-drug by different cell types in the hippocampus after hypoxic-ischemic insult in neonatal mice: Effects of injury, microglial activation and hypothermia. Nanomedicine 13: 2359-2369. doi: 10.1016/j.nano.2017.06.014
    [135] Zhang F, Trent MJ, Lin YA, et al. (2017) Generation-6 hydroxyl PAMAM dendrimers improve CNS penetration from intravenous administration in a large animal brain injury model. J Control Release 249: 173-182. doi: 10.1016/j.jconrel.2017.01.032
    [136] Balcer LJ, Galetta SL, Calabresi PA, et al. (2007) Natalizumab reduces visual loss in patients with relapsing multiple sclerosis. Neurology 68: 1299-1304. doi: 10.1212/01.wnl.0000259521.14704.a8
    [137] Sättler MB, Demmer I, Williams SK, et al. (2006) Effects of interferon-beta-1a on neuronal survival under autoimmune inflammatory conditions. Exp Neurol 201: 172-181. doi: 10.1016/j.expneurol.2006.04.015
    [138] Coleman M (2005) Axon degeneration mechanisms: commonality amid diversity. Nat Rev Neurosci 6: 889-898. doi: 10.1038/nrn1788
  • Reader Comments
  • © 2017 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)
通讯作者: 陈斌, bchen63@163.com
  • 1. 

    沈阳化工大学材料科学与工程学院 沈阳 110142

  1. 本站搜索
  2. 百度学术搜索
  3. 万方数据库搜索
  4. CNKI搜索
AIMS Molecular Science
0.7

Metrics

Article views(4950) PDF downloads(1042) Cited by(2)

Preview PDF
Download XML
Export Citation
Article outline

Figures and Tables

Tables(1)

Other Articles By Authors

Related pages

Tools

/

DownLoad:  Full-Size Img  PowerPoint
Return
Return

Catalog