Endoplasmic reticulum stress and the unfolded protein response in disorders of myelinating glia

Brain Research

Volumn 1648, Issue , 2016, Pages 594-602

  Clayton, Benjamin L L ^a   Popko, Brian ^a  

^a The University of Chicago Pritzker School of Medicine   (United States)

Author keywords

ER stress; Myelin; Oligodendrocytes; Schwann cells; Unfolded protein response

Indexed keywords

ACTIVATING TRANSCRIPTION FACTOR 6; GAMMA INTERFERON; GROWTH ARREST AND DNA DAMAGE INDUCIBLE PROTEIN 153; INITIATION FACTOR 2ALPHA; PROTEIN BCL 2; PROTEIN IRE1; PROTEOLIPID PROTEIN; X BOX BINDING PROTEIN 1; ALPHA 2 ADRENERGIC RECEPTOR STIMULATING AGENT; GUANABENZ; SEPHIN1;

AMINO ACID SUBSTITUTION; APOPTOSIS; CELL SURVIVAL; DEMYELINATING DISEASE; ENDOPLASMIC RETICULUM STRESS; GENE EXPRESSION; HEREDITARY MOTOR SENSORY NEUROPATHY; HUMAN; IMMUNOREACTIVITY; MULTIPLE SCLEROSIS; NEUROPATHOLOGY; NONHUMAN; PELIZAEUS MERZBACHER DISEASE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FOLDING; PROTEIN LOCALIZATION; PROTEIN PHOSPHORYLATION; REVIEW; UNFOLDED PROTEIN RESPONSE; WHITE MATTER LESION; ANALOGS AND DERIVATIVES; ANIMAL; DRUG EFFECTS; GLIA; METABOLISM; PATHOLOGY; PHYSIOLOGY;

ADRENERGIC ALPHA-2 RECEPTOR AGONISTS; ANIMALS; DEMYELINATING DISEASES; ENDOPLASMIC RETICULUM STRESS; GUANABENZ; HUMANS; NEUROGLIA; UNFOLDED PROTEIN RESPONSE;

EID: 84963865012     PISSN: 00068993     EISSN: 18726240     Source Type: Journal    
DOI: 10.1016/j.brainres.2016.03.046     Document Type: Review

References (81)

1. Baba, H., Akita, H., Ishibashi, T., Inoue, Y., Nakahira, K., Ikenaka, K., Completion of myelin compaction, but not the attachment of oligodendroglial processes triggers K+ channel clustering. J Neurosci. Res., 1999.
2. Bai, Y., Patzko, A., Shy, M.E., 2013. Unfolded protein response, treatment and CMT1B. Rare diseases (Austin, Tex.) 1, e24049. 10.4161/rdis.24049.
3. Barnett, M.H., Prineas, J.W., Relapsing and remitting multiple sclerosis: pathology of the newly forming lesion. Ann. Neurol. 55 (2004), 458–468, 10.1002/ana.20016.
4. Bercury, K.K., Macklin, W.B., Dynamics and mechanisms of CNS myelination. Dev. Cell 32 (2015), 447–458, 10.1016/j.devcel.2015.01.016.
5. Boyce, M., Bryant, K.F., Jousse, C., Long, K., Harding, H.P., Scheuner, D., Kaufman, R.J., Ma, D., Coen, D.M., Ron, D., Yuan, J., A selective inhibitor of eIF2alpha dephosphorylation protects cells from ER stress. Science 307 (2005), 935–939, 10.1126/science.1101902.
6. Buttermore, E.D., Thaxton, C.L., Bhat, M.A., Organization and maintenance of molecular domains in myelinated axons. J. Neurosci. Res. 91 (2013), 603–622, 10.1002/jnr.23197.
7. Calfon, M., Zeng, H., Urano, F., Till, J.H., Hubbard, S.R., Harding, H.P., Clark, S.G., Ron, D., IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA. Nature 415 (2002), 92–96, 10.1038/415092a.
8. Cao, S.S., Kaufman, R.J., Unfolded protein response. Curr. Biol. 22 (2012), R622–R626, 10.1016/j.cub.2012.07.004.
9. Chakrabarty, A., Danley, M.M., LeVine, S.M., Immunohistochemical localization of phosphorylated protein kinase R and phosphorylated eukaryotic initiation factor-2 alpha in the central nervous system of SJL mice with experimental allergic encephalomyelitis. J. Neurosci. Res. 76 (2004), 822–833, 10.1002/jnr.20125.
10. Chakrabarty, A., Fleming, K.K., Marquis, J.G., LeVine, S.M., Quantifying immunohistochemical staining of phospho-eIF2alpha, heme oxygenase-2 and NADPH cytochrome P450 reductase in oligodendrocytes during experimental autoimmune encephalomyelitis. J. Neurosci. Methods 144 (2005), 227–234, 10.1016/j.jneumeth.2004.11.010.
11. Chen, N., Jiang, Y.W., Hao, H.J., Ban, T.T., Gao, K., Zhang, Z.B., Wang, J.M., Wu, Y., Different Eukaryotic Initiation Factor 2Bε Mutations Lead to Various Degrees of Intolerance to the Stress of Endoplasmic Reticulum in Oligodendrocytes. Chin. Med. J. 128 (2015), 1772–1777, 10.4103/0366-6999.159353.
12. Ching, W., Zanazzi, G., Levinson, S.R., Salzer, J.L., Clustering of neuronal sodium channels requires contact with myelinating Schwann cells. J. Neurocytol. 28 (1999), 295–301.
13. Cunnea, P., Mháille, A.N., McQuaid, S., Farrell, M., McMahon, J., FitzGerald, U., Expression profiles of endoplasmic reticulum stress-related molecules in demyelinating lesions and multiple sclerosis. Mult. Scler. 17 (2011), 808–818, 10.1177/1352458511399114.
14. D'Antonio, M., Feltri, M.L., Wrabetz, L., Myelin under stress. J. Neurosci. Res. 87 (2009), 3241–3249, 10.1002/jnr.22066.
15. D'Antonio, M., Musner, N., Scapin, C., Ungaro, D., Del Carro, U., Ron, D., Feltri, M.L., Wrabetz, L., Resetting translational homeostasis restores myelination in Charcot-Marie-Tooth disease type 1B mice. J. Exp. Med. 210 (2013), 821–838, 10.1084/jem.20122005.
16. Das, I., Krzyzosiak, A., Schneider, K., Wrabetz, L., D'Antonio, M., Barry, N., Sigurdardottir, A., Bertolotti, A., Preventing proteostasis diseases by selective inhibition of a phosphatase regulatory subunit. Science 348 (2015), 239–242, 10.1126/science.aaa4484.
17. Deslauriers, A.M., Afkhami-Goli, A., Paul, A.M., Bhat, R.K., Acharjee, S., Ellestad, K.K., Noorbakhsh, F., Michalak, M., Power, C., Neuroinflammation and endoplasmic reticulum stress are coregulated by crocin to prevent demyelination and neurodegeneration. J. Immunol. 187 (2011), 4788–4799, 10.4049/jimmunol.1004111.
18. Dickson, K.M., Bergeron, J.J., Shames, I., Colby, J., Nguyen, D.T., Chevet, E., Thomas, D.Y., Snipes, G.J., Association of calnexin with mutant peripheral myelin protein-22 ex vivo: a basis for “gain-of-function” ER diseases. Proc. Natl. Acad. Sci. USA 99 (2002), 9852–9857, 10.1073/pnas.152621799.
19. Franklin, R.J., ffrench-Constant, C., Edgar, J.M., Smith, K.J., Neuroprotection and repair in multiple sclerosis. Nat. Rev. Neurol. 8 (2012), 624–634, 10.1038/nrneurol.2012.200.
20. Fünfschilling, U., Supplie, L.M., Mahad, D., Boretius, S., Saab, A.S., Edgar, J., Brinkmann, B.G., Kassmann, C.M., Tzvetanova, I.D., Möbius, W., Diaz, F., Meijer, D., Suter, U., Hamprecht, B., Sereda, M.W., Moraes, C.T., Frahm, J., Goebbels, S., Nave, K.A., Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity. Nature 485 (2012), 517–521, 10.1038/nature11007.
21. Garbern, J.Y., Pelizaeus-Merzbacher disease: Genetic and cellular pathogenesis. Cell. Mol. Life Sci. 64 (2007), 50–65, 10.1007/s00018-006-6182-8.
22. Geva, M., Cabilly, Y., Assaf, Y., Mindroul, N., Marom, L., Raini, G., Pinchasi, D., Elroy-Stein, O., A mouse model for eukaryotic translation initiation factor 2B-leucodystrophy reveals abnormal development of brain white matter. Brain 133 (2010), 2448–2461, 10.1093/brain/awq180.
23. Gow, A., Lazzarini, R.A., A cellular mechanism governing the severity of Pelizaeus-Merzbacher disease. Nat. Genet. 13 (1996), 422–428, 10.1038/ng0896-422.
24. Greer, J.M., Lees, M.B., Myelin proteolipid protein – the first 50 years. Int. J. Biochem. Cell Biol. 34 (2002), 211–215, 10.1016/S1357-2725(01)00136-4.
25. Griffiths, I., Klugmann, M., Anderson, T., Yool, D., Thomson, C., Schwab, M.H., Schneider, A., Zimmermann, F., McCulloch, M., Nadon, N., Nave, K.A., Axonal swellings and degeneration in mice lacking the major proteolipid of myelin. Science 280 (1998), 1610–1613.
26. Harding, H.P., Zhang, Y., Ron, D., Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase. Nature 397 (1999), 271–274, 10.1038/16729.
27. Harding, H.P., Zhang, Y., Zeng, H., Novoa, I., Lu, P.D., Calfon, M., Sadri, N., Yun, C., Popko, B., Paules, R., Stojdl, D.F., Bell, J.C., Hettmann, T., Leiden, J.M., Ron, D., An integrated stress response regulates amino acid metabolism and resistance to oxidative stress. Mol. Cell 11 (2003), 619–633.
28. Hollien, J., Weissman, J.S., Decay of endoplasmic reticulum-localized mRNAs during the unfolded protein response. Science 313 (2006), 104–107, 10.1126/science.1129631.
29. Hoyle, J.C., Isfort, M.C., Roggenbuck, J., Arnold, W.D., The genetics of Charcot-Marie-Tooth disease: current trends and future implications for diagnosis and management. Appl. Clin. Genet. 8 (2015), 235–243, 10.2147/TACG.S69969.
30. Hussien, Y., Cavener, D.R., Popko, B., Genetic inactivation of PERK signaling in mouse oligodendrocytes: normal developmental myelination with increased susceptibility to inflammatory demyelination. Glia 62 (2014), 680–691, 10.1002/glia.22634.
31. Hussien, Y., Podojil, J.R., Robinson, A.P., Lee, A.S., Miller, S.D., Popko, B., ER chaperone BiP/GRP78 is required for myelinating cell survival and provides protection during experimental autoimmune encephalomyelitis. J Neurosci. 35 (2015), 15921–15933, 10.1523/JNEUROSCI.0693-15.2015.
32. Kantor, L., Pinchasi, D., Mintz, M., Hathout, Y., Vanderver, A., Elroy-Stein, O., A point mutation in translation initiation factor 2B leads to a continuous hyper stress state in oligodendroglial-derived cells. PLoS One, 3, 2008, e3783, 10.1371/journal.pone.0003783.
33. Karussis, D., The diagnosis of multiple sclerosis and the various related demyelinating syndromes: a critical review. J. Autoimmun., 2014, 10.1016/j.jaut.2014.01.022.
34. Klugmann, M., Schwab, M.H., Pühlhofer, A., Schneider, A., Zimmermann, F., Griffiths, I.R., Nave, K.A., Assembly of CNS myelin in the absence of proteolipid protein. Neuron 18 (1997), 59–70, 10.1016/S0896-6273(01)80046-5.
35. Lappe-Siefke, C., Goebbels, S., Gravel, M., Nicksch, E., Lee, J., Braun, P.E., Griffiths, I.R., Nave, K.A., Disruption of Cnp1 uncouples oligodendroglial functions in axonal support and myelination. Nat. Genet. 33 (2003), 366–374, 10.1038/ng1095.
36. Lee, Y., Morrison, B.M., Li, Y., Lengacher, S., Farah, M.H., Hoffman, P.N., Liu, Y., Tsingalia, A., Jin, L., Zhang, P.W., Pellerin, L., Magistretti, P.J., Rothstein, J.D., Oligodendroglia metabolically support axons and contribute to neurodegeneration. Nature 487 (2012), 443–448, 10.1038/nature11314.
37. Lees, J.R., Cross, A.H., A little stress is good: IFN-gamma, demyelination, and multiple sclerosis. J. Clin. Investig. 117 (2007), 297–299, 10.1172/JCI31254.
38. Li, Y., Guo, Y., Tang, J., Jiang, J., Chen, Z., New insights into the roles of CHOP-induced apoptosis in ER stress. Acta Biochim. Biophys. Sin., 2014, 10.1093/abbs/gmu048.
39. Lin, W., Bailey, S.L., Ho, H., Harding, H.P., Ron, D., Miller, S.D., Popko, B., The integrated stress response prevents demyelination by protecting oligodendrocytes against immune-mediated damage. J. Clin. Investig. 117 (2007), 448–456, 10.1172/JCI29571.
40. Lin, W., Harding, H.P., Ron, D., Popko, B., Endoplasmic reticulum stress modulates the response of myelinating oligodendrocytes to the immune cytokine interferon-gamma. J. Cell Biol. 169 (2005), 603–612, 10.1083/jcb.200502086.
41. Lin, W., Kemper, A., Dupree, J.L., Harding, H.P., Ron, D., Popko, B., Interferon-gamma inhibits central nervous system remyelination through a process modulated by endoplasmic reticulum stress. Brain 129 (2006), 1306–1318, 10.1093/brain/awl044.
42. Lin, W., Kunkler, P.E., Harding, H.P., Ron, D., Kraig, R.P., Popko, B., Enhanced integrated stress response promotes myelinating oligodendrocyte survival in response to interferon-gamma. Am. J. Pathol. 173 (2008), 1508–1517, 10.2353/ajpath.2008.080449.
43. Lin, W., Lin, Y., Li, J., Fenstermaker, A.G., Way, S.W., Clayton, B., Jamison, S., Harding, H.P., Ron, D., Popko, B., Oligodendrocyte-specific activation of PERK signaling protects mice against experimental autoimmune encephalomyelitis. J. Neurosci. 33 (2013), 5980–5991, 10.1523/JNEUROSCI.1636-12.2013.
44. Lin, W., Popko, B., Endoplasmic reticulum stress in disorders of myelinating cells. Nat. Neurosci. 12 (2009), 379–385, 10.1038/nn.2273.
45. Lin, Y., Huang, G., Jamison, S., Li, J., Harding, H.P., Ron, D., Lin, W., PERK activation preserves the viability and function of remyelinating oligodendrocytes in immune-mediated demyelinating diseases. Am. J. Pathol. 184 (2014), 507–519, 10.1016/j.ajpath.2013.10.009.
46. Lin, Y., Pang, X., Huang, G., Jamison, S., Fang, J., Harding, H.P., Ron, D., Lin, W., Impaired eukaryotic translation initiation factor 2B activity specifically in oligodendrocytes reproduces the pathology of vanishing white matter disease in mice. J. Neurosci. 34 (2014), 12182–12191, 10.1523/JNEUROSCI.1373-14.2014.
47. Lossos, A., Elazar, N., Lerer, I., Schueler-Furman, O., Fellig, Y., Glick, B., Zimmerman, B.E., Azulay, H., Dotan, S., Goldberg, S., Gomori, J.M., Ponger, P., Newman, J.P., Marreed, H., Steck, A.J., Schaeren-Wiemers, N., Mor, N., Harel, M., Geiger, T., Eshed-Eisenbach, Y., Meiner, V., Peles, E., Myelin-associated glycoprotein gene mutation causes Pelizaeus-Merzbacher disease-like disorder. Brain 138 (2015), 2521–2536, 10.1093/brain/awv204.
48. Marciniak, S.J., Yun, C.Y., Oyadomari, S., Novoa, I., Zhang, Y., Jungreis, R., Nagata, K., Harding, H.P., Ron, D., CHOP induces death by promoting protein synthesis and oxidation in the stressed endoplasmic reticulum. Genes Dev. 18 (2004), 3066–3077, 10.1101/gad.1250704.
49. McMahon, J.M., McQuaid, S., Reynolds, R., FitzGerald, U.F., Increased expression of ER stress- and hypoxia-associated molecules in grey matter lesions in multiple sclerosis. Mult. Scler. 18 (2012), 1437–1447, 10.1177/1352458512438455.
50. Mháille, A.N., McQuaid, S., Windebank, A., Cunnea, P., McMahon, J., Samali, A., FitzGerald, U., Increased expression of endoplasmic reticulum stress-related signaling pathway molecules in multiple sclerosis lesions. J. Neuropathol. Exp. Neurol. 67 (2008), 200–211, 10.1097/NEN.0b013e318165b239.
51. Morrison, B.M., Lee, Y., Rothstein, J.D., Oligodendroglia: metabolic supporters of axons. Trends Cell. Biol. 23 (2013), 644–651, 10.1016/j.tcb.2013.07.007.
52. Ní Fhlathartaigh, M., McMahon, J., Reynolds, R., Connolly, D., Higgins, E., Counihan, T., Fitzgerald, U., Calreticulin and other components of endoplasmic reticulum stress in rat and human inflammatory demyelination. Acta Neuropathol. Commun., 1, 2013, 37, 10.1186/2051-5960-1-37.
53. Novoa, I., Zeng, H., Harding, H.P., Ron, D., Feedback inhibition of the unfolded protein response by GADD34-mediated dephosphorylation of eIF2alpha. J. Cell Biol. 153 (2001), 1011–1022.
54. Numasawa-Kuroiwa, Y., Okada, Y., Shibata, S., Kishi, N., Akamatsu, W., Shoji, M., Nakanishi, A., Oyama, M., Osaka, H., Inoue, K., Takahashi, K., Yamanaka, S., Kosaki, K., Takahashi, T., Okano, H., Involvement of ER stress in dysmyelination of Pelizaeus–Merzbacher disease with PLP1 missense mutations shown by iPSC-derived oligodendrocytes. Stem Cell Rep. 2 (2014), 648–661, 10.1016/j.stemcr.2014.03.007.
55. Patzkó, A., Bai, Y., Saporta, M.A., Katona, I., Wu, X., Vizzuso, D., Feltri, M.L., Wang, S., Dillon, L.M., Kamholz, J., Kirschner, D., Sarkar, F.H., Wrabetz, L., Shy, M.E., Curcumin derivatives promote Schwann cell differentiation and improve neuropathy in R98C CMT1B mice. Brain 135 (2012), 3551–3566, 10.1093/brain/aws299.
56. Pavitt, G.D., Ron, D., New insights into translational regulation in the endoplasmic reticulum unfolded protein response. Cold Spring Harb. Perspect. Biol., 2012, 4, 10.1101/cshperspect.a012278.
57. Pennuto, M., Tinelli, E., Malaguti, M., Del Carro, U., D'Antonio, M., Ron, D., Quattrini, A., Feltri, M.L., Wrabetz, L., Ablation of the UPR-mediator CHOP restores motor function and reduces demyelination in Charcot-Marie-Tooth 1B mice. Neuron 57 (2008), 393–405, 10.1016/j.neuron.2007.12.021.
58. Peschek, J., Acosta-Alvear, D., Mendez, A.S., Walter, P., A conformational RNA zipper promotes intron ejection during non-conventional XBP1 mRNA splicing. EMBO Rep. 16 (2015), 1688–1698, 10.15252/embr.201540955.
59. Pfeiffer, S.E., Warrington, A.E., Bansal, R., The oligodendrocyte and its many cellular processes. Trends Cell. Biol. 3 (1993), 191–197.
60. Popko, B., Corbin, J.G., Baerwald, K.D., Dupree, J., Garcia, A.M., The effects of interferon-gamma on the central nervous system. Mol. Neurobiol. 14 (1997), 19–35, 10.1007/BF02740619.
61. Rasband, M.N., Peles, E., Trimmer, J.S., Levinson, S.R., Lux, S.E., Shrager, P., Dependence of nodal sodium channel clustering on paranodal axoglial contact in the developing CNS. J. Neurosci. 19 (1999), 7516–7528.
62. Rinholm, J.E., Hamilton, N.B., Kessaris, N., Richardson, W.D., Bergersen, L.H., Attwell, D., Regulation of oligodendrocyte development and myelination by glucose and lactate. J. Neurosci. 31 (2011), 538–548, 10.1523/JNEUROSCI.3516-10.2011.
63. Rosenbluth, J., Nave, K.A., Mierzwa, A., Schiff, R., Subtle myelin defects in PLP-null mice. Glia 54 (2006), 172–182, 10.1002/glia.20370.
64. Saporta, M.A., Shy, B.R., Patzko, A., Bai, Y., Pennuto, M., Ferri, C., Tinelli, E., Saveri, P., Kirschner, D., Crowther, M., Southwood, C., Wu, X., Gow, A., Feltri, M.L., Wrabetz, L., Shy, M.E., MpzR98C arrests Schwann cell development in a mouse model of early-onset Charcot-Marie-Tooth disease type 1B. Brain 135 (2012), 2032–2047, 10.1093/brain/aws140.
65. Shen, X., Ellis, R.E., Sakaki, K., Kaufman, R.J., Genetic interactions due to constitutive and inducible gene regulation mediated by the unfolded protein response in C. elegans. PLoS Genet., 1, 2005, e37, 10.1371/journal.pgen.0010037.
66. Simons, M., Nave, K.A., Oligodendrocytes: Myelination and Axonal Support. Cold Spring Harb. Perspect. Biol., 2015, 10.1101/cshperspect.a020479.
67. Southwood, C.M., Fykkolodziej, B., Dachet, F., Gow, A., Potential for cell-mediated immune responses in mouse models of Pelizaeus–Merzbacher disease. Brain Sci. 3 (2013), 1417–1444, 10.3390/brainsci3041417.
68. Southwood, C.M., Garbern, J., Jiang, W., Gow, A., The unfolded protein response modulates disease severity in Pelizaeus–Merzbacher disease. Neuron 36 (2002), 585–596, 10.1016/S0896-6273(02)01045-0.
69. Stone, S., Lin, W., The unfolded protein response in multiple sclerosis. Front. Neurosci., 9, 2015, 264, 10.3389/fnins.2015.00264.
70. Theocharopoulou, G., Vlamos, P., Modeling protein misfolding in charcot-marie-tooth disease. Adv. Exp. Med. Biol. 820 (2015), 91–102, 10.1007/978-3-319-09012-2_7.
71. Traka, M., Podojil, J.R., McCarthy, D.P., Miller, S.D., Popko, B., Oligodendrocyte death results in immune-mediated CNS demyelination. Nat. Neurosci., 2015, 10.1038/nn.4193.
72. Tsaytler, P., Harding, H.P., Ron, D., Bertolotti, A., Selective inhibition of a regulatory subunit of protein phosphatase 1 restores proteostasis. Science 332 (2011), 91–94, 10.1126/science.1201396.
73. Van der Knaap, M.S., Pronk, J.C., Scheper, G.C., Vanishing white matter disease. Lancet Neurol. 5 (2006), 413–423, 10.1016/S1474-4422(06)70440-9.
74. Van der Voorn, J.P., van Kollenburg, B., Bertrand, G., Van Haren, K., Scheper, G.C., Powers, J.M., van der Knaap, M.S., The unfolded protein response in vanishing white matter disease. J. Neuropathol. Exp. Neurol. 64 (2005), 770–775, 10.1097/01.jnen.0000178446.41595.3a.
75. Van Kollenburg, B., van Dijk, J., Garbern, J., Thomas, A.A., Scheper, G.C., Powers, J.M., van der Knaap, M.S., Glia-specific activation of all pathways of the unfolded protein response in vanishing white matter disease. J. Neuropathol. Exp. Neurol. 65 (2006), 707–715, 10.1097/01.jnen.0000228201.27539.50.
76. Walter, P., Ron, D., The unfolded protein response: from stress pathway to homeostatic regulation. Science 334 (2011), 1081–1086, 10.1126/science.1209038.
77. Way, S.W., Podojil, J.R., Clayton, B.L., Zaremba, A., Collins, T.L., Kunjamma, R.B., Robinson, A.P., Brugarolas, P., Miller, R.H., Miller, S.D., Popko, B., Pharmaceutical integrated stress response enhancement protects oligodendrocytes and provides a potential multiple sclerosis therapeutic. Nat. Commun., 6, 2015, 6532, 10.1038/ncomms7532.
78. Way, S.W., Popko, B., Harnessing the integrated stress response for the treatment of multiple sclerosis. Lancet Neurol. 15 (2016), 434–443, 10.1016/S1474-4422(15)00381-6.
79. Wrabetz, L., D'Antonio, M., Pennuto, M., Dati, G., Tinelli, E., Fratta, P., Previtali, S., Imperiale, D., Zielasek, J., Toyka, K., Avila, R.L., Kirschner, D.A., Messing, A., Feltri, M.L., Quattrini, A., Different intracellular pathomechanisms produce diverse Myelin Protein Zero neuropathies in transgenic mice. J. Neurosci. 26 (2006), 2358–2368, 10.1523/JNEUROSCI.3819-05.2006.
80. Ye, J., Rawson, R.B., Komuro, R., Chen, X., Davé, U.P., Prywes, R., Brown, M.S., Goldstein, J.L., ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs. Mol. Cell. 6 (2000), 1355–1364.
81. Zinszner, H., Kuroda, M., Wang, X., Batchvarova, N., Lightfoot, R.T., Remotti, H., Stevens, J.L., Ron, D., CHOP is implicated in programmed cell death in response to impaired function of the endoplasmic reticulum. Genes. Dev. 12 (1998), 982–995.