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Cytoskeleton and Human Disease pp 425–448Cite as

Neurodegenerative Diseases and Intermediate Filaments

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Abstract

Intermediate filaments (IFs) represent the most abundant cytoskeletal constituent in mature neurons. Their mutations and/or accumulations are associated with many human neurodegenerative disorders and it is now well established that disorganization of the intermediate filament network may be directly involved in neurodegeneration. Diseases caused by intermediate filament abnormalities show a wide range of phenotypes, depending on many factors, including the class of affected intermediate filaments and the type of mutation. Various mouse models were extensively used to provide a better understanding of the role played by the disorganization of intermediate filaments in the pathogenesis of neurodegenerative disorders. However, the mechanisms leading to the formation of these aggregates often remain elusive. Multiple factors can potentially induce the accumulation of neuronal intermediate filaments, including dysregulation of intermediate filament gene expression, intermediate filament mutations, defective axonal transport, abnormal posttranslational modifications, and/or proteolysis. Here, we review some neurodegenerative diseases involving intermediate filament abnormalities and possible mechanisms susceptible to provoke them.

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References

  1. Julien JP, Mushynski WE (1998) Neurofilaments in health and disease. Prog Nucleic Acid Res Mol Biol 61:1–23

    Article  PubMed  CAS  Google Scholar 

  2. Yuan A, Rao MV, Sasaki T, Chen Y, Kumar A, Veeranna V, Liem RK, Eyer J, Peterson AC, Julien JP, Nixon RA (2006) Alpha-internexin is structurally and functionally associated with the neurofilament triplet proteins in the mature CNS. J Neurosci 26:10006–10019

    Article  PubMed  CAS  Google Scholar 

  3. Yan Y, Jensen K, Brown A (2007) The polypeptide composition of moving and stationary neurofilaments in cultured sympathetic neurons. Cell Motil Cytoskeleton 64:299–309

    Article  PubMed  CAS  Google Scholar 

  4. Perrot R, Berges R, Bocquet A, Eyer J (2008) Review of the multiple aspects of neurofilament functions, and their possible contribution to neurodegeneration. Mol Neurobiol 38:27–65

    Article  PubMed  CAS  Google Scholar 

  5. Nixon RA, Shea TB (1992) Dynamics of neuronal intermediate filaments: a developmental perspective. Cell Motil Cytoskeleton 22:81–91

    Article  PubMed  CAS  Google Scholar 

  6. Fuchs E, Weber K (1994) Intermediate filaments: structure, dynamics, function, and disease. Annu Rev Biochem 63:345–382

    Article  PubMed  CAS  Google Scholar 

  7. Perrot R, Eyer J (2009) Neuronal intermediate filaments and neurodegenerative disorders. Brain Res Bull 80:282–295

    Article  PubMed  CAS  Google Scholar 

  8. Quinlan RA, Brenner M, Goldman JE, Messing A (2007) GFAP and its role in Alexander disease. Exp Cell Res 313:2077–2087

    Article  PubMed  CAS  Google Scholar 

  9. Figlewicz DA, Krizus A, Martinoli MG, Meininger V, Dib M, Rouleau GA, Julien JP (1994) Variants of the Heavy Neurofilament Subunit Are Associated with the Development of Amyotrophic-Lateral-Sclerosis. Hum Mol Genet 3:1757–1761

    Article  PubMed  CAS  Google Scholar 

  10. Tomkins J, Usher P, Slade JY, Ince PG, Curtis A, Bushby K, Shaw PJ (1998) Novel insertion in the KSP region of the neurofilament heavy gene in amyotrophic lateral sclerosis (ALS). Neuroreport 9:3967–3970

    Article  PubMed  CAS  Google Scholar 

  11. Al-Chalabi A, Andersen PM, Nilsson P, Chioza B, Andersson JL, Russ C, Shaw CE, Powell JF, Leigh PN (1999) Deletions of the heavy neurofilament subunit tail in amyotrophic lateral sclerosis. Hum Mol Genet 8:157–164

    Article  PubMed  CAS  Google Scholar 

  12. Rooke K, Figlewicz DA, Han FY, Rouleau GA (1996) Analysis of the KSP repeat of the neurofilament heavy subunit in familial amyotrophic lateral sclerosis. Neurology 46:789–790

    Article  PubMed  CAS  Google Scholar 

  13. Vechio JD, Bruijn LI, Xu ZS, Brown RH, Cleveland DW (1996) Sequence variants in human neurofilament proteins: Absence of linkage to familial amyotrophic lateral sclerosis. Ann Neurol 40:603–610

    Article  PubMed  CAS  Google Scholar 

  14. Gros-Louis F, Lariviere R, Gowing G, Laurent S, Camu W, Bouchard JP, Meininger V, Rouleau GA, Julien JP (2004) A frameshift deletion in peripherin gene associated with amyotrophic lateral sclerosis. J Biol Chem 279:45951–45956

    Article  PubMed  CAS  Google Scholar 

  15. Leung CL, He CZ, Kaufmann P, Chin SS, Naini A, Liem RKH, Mitsumoto H, Hays AP (2004) A pathogenic peripherin gene mutation in a patient with amyotrophic lateral sclerosis. Brain Pathol 14:290–296

    Article  PubMed  CAS  Google Scholar 

  16. Corrado L, Carlomagno Y, Falasco L, Mellone S, Godi M, Cova E, Cereda C, Testa L, Mazzini L, D’Alfonso S (2011) A novel peripherin gene (PRPH) mutation identified in one sporadic amyotrophic lateral sclerosis patient. Neurobiol Aging 32(3):552, e1–e6

    Article  PubMed  CAS  Google Scholar 

  17. Xiao S, Tjostheim S, Sanelli T, McLean JR, Horne P, Fan Y, Ravits J, Strong MJ, Robertson J (2008) An aggregate-inducing peripherin isoform generated through intron retention is upregulated in amyotrophic lateral sclerosis and associated with disease pathology. J Neurosci 28:1833–1840

    Article  PubMed  CAS  Google Scholar 

  18. Robertson J, Doroudchi MM, Nguyen MD, Durham HD, Strong MJ, Shaw G, Julien JP, Mushynski WE (2003) A neurotoxic peripherin splice variant in a mouse model of ALS. J Cell Biol 160:939–949

    Article  PubMed  CAS  Google Scholar 

  19. Niebroj-Dobosz I, Dziewulska D, Janik P (2006) Auto-antibodies against proteins of spinal cord cells in cerebrospinal fluid of patients with amyotrophic lateral sclerosis (ALS). Folia Neuropathol 44:191–196

    PubMed  CAS  Google Scholar 

  20. Zetterberg H, Jacobsson J, Rosengren L, Blennow K, Andersen PM (2007) Cerebrospinal fluid neurofilament light levels in amyotrophic lateral sclerosis: impact of SOD1 genotype. Eur J Neurol 14:1329–1333

    Article  PubMed  CAS  Google Scholar 

  21. Brettschneider J, Petzold A, Sussmuth SD, Ludolph AC, Tumani H (2006) Axonal damage markers in cerebrospinal fluid are increased in ALS. Neurology 66:852–856

    Article  PubMed  CAS  Google Scholar 

  22. Corbo M, Hays AP (1992) Peripherin and neurofilament protein coexist in spinal spheroids of motor neuron disease. J Neuropathol Exp Neurol 51:531–537

    Article  PubMed  CAS  Google Scholar 

  23. Manetto V, Sternberger NH, Perry G, Sternberger LA, Gambetti P (1988) Phosphorylation of neurofilaments is altered in amyotrophic lateral sclerosis. J Neuropathol Exp Neurol 47:642–653

    Article  PubMed  CAS  Google Scholar 

  24. Collard JF, Cote F, Julien JP (1995) Defective axonal transport in a transgenic mouse model of amyotrophic lateral sclerosis. Nature 375:61–64

    Article  PubMed  CAS  Google Scholar 

  25. Williamson TL, Cleveland DW (1999) Slowing of axonal transport is a very early event in the toxicity of ALS-linked SOD1 mutants to motor neurons. Nat Neurosci 2:50–56

    Article  PubMed  CAS  Google Scholar 

  26. Zhang B, Tu P, Abtahian F, Trojanowski JQ, Lee VM (1997) Neurofilaments and orthograde transport are reduced in ventral root axons of transgenic mice that express human SOD1 with a G93A mutation. J Cell Biol 139:1307–1315

    Article  PubMed  CAS  Google Scholar 

  27. Bilsland LG, Sahai E, Kelly G, Golding M, Greensmith L, Schiavo G (2010) Deficits in axonal transport precede ALS symptoms in vivo. Proc Natl Acad Sci U S A 107:20523–20528

    Article  PubMed  CAS  Google Scholar 

  28. Ackerley S, Grierson AJ, Brownlees J, Thornhill P, Anderton BH, Leigh PN, Shaw CE, Miller CC (2000) Glutamate slows axonal transport of neurofilaments in transfected neurons. J Cell Biol 150:165–176

    Article  PubMed  CAS  Google Scholar 

  29. Manser C, Stevenson A, Banner S, Davies J, Tudor EL, Ono Y, Leigh PN, McLoughlin DM, Shaw CE, Miller CC (2008) Deregulation of PKN1 activity disrupts neurofilament organisation and axonal transport. FEBS Lett 582:2303–2308

    Article  PubMed  CAS  Google Scholar 

  30. King AE, Dickson TC, Blizzard CA, Foster SS, Chung RS, West AK, Chuah MI, Vickers JC (2007) Excitotoxicity mediated by non-NMDA receptors causes distal axonopathy in long-term cultured spinal motor neurons. Eur J Neurosci 26:2151–2159

    Article  PubMed  CAS  Google Scholar 

  31. Kesavapany S, Patel V, Zheng YL, Pareek TK, Bjelogrlic M, Albers W, Amin N, Jaffe H, Gutkind JS, Strong MJ, Grant P, Pant HC (2007) Inhibition of Pin1 reduces glutamate-induced perikaryal accumulation of phosphorylated neurofilament-H in neurons. Mol Biol Cell 18:3645–3655

    Article  PubMed  CAS  Google Scholar 

  32. Stevenson A, Yates DM, Manser C, De Vos KJ, Vagnoni A, Leigh PN, McLoughlin DM, Miller CC (2009) Riluzole protects against glutamate-induced slowing of neurofilament axonal transport. Neurosci Lett 454:161–164

    Article  PubMed  CAS  Google Scholar 

  33. Hafezparast M, Klocke R, Ruhrberg C, Marquardt A, Ahmad-Annuar A, Bowen S, Lalli G, Witherden AS, Hummerich H, Nicholson S, Morgan PJ, Oozageer R, Priestley JV, Averill S, King VR, Ball S, Peters J, Toda T, Yamamoto A, Hiraoka Y, Augustin M, Korthaus D, Wattler S, Wabnitz P, Dickneite C, Lampel S, Boehme F, Peraus G, Popp A, Rudelius M, Schlegel J, Fuchs H, Hrabe de AM, Schiavo G, Shima DT, Russ AP, Stumm G, Martin JE, Fisher EM (2003) Mutations in dynein link motor neuron degeneration to defects in retrograde transport. Science 300:808–812

    Article  PubMed  CAS  Google Scholar 

  34. LaMonte BH, Wallace KE, Holloway BA, Shelly SS, Ascano J, Tokito M, Van Winkle T, Howland DS, Holzbaur EL (2002) Disruption of dynein/dynactin inhibits axonal transport in motor neurons causing late-onset progressive degeneration. Neuron 34:715–727

    Article  PubMed  CAS  Google Scholar 

  35. Xia CH, Roberts EA, Her LS, Liu X, Williams DS, Cleveland DW, Goldstein LS (2003) Abnormal neurofilament transport caused by targeted disruption of neuronal kinesin heavy chain KIF5A. J Cell Biol 161:55–66

    Article  PubMed  CAS  Google Scholar 

  36. Motil J, Dubey M, Chan WK, Shea TB (2007) Inhibition of dynein but not kinesin induces aberrant focal accumulation of neurofilaments within axonal neurites. Brain Res 1164:125–131

    Article  PubMed  CAS  Google Scholar 

  37. Teuling E, van Dis V, Wulf PS, Haasdijk ED, Akhmanova A, Hoogenraad CC, Jaarsma D (2008) A novel mouse model with impaired dynein/dynactin function develops amyotrophic lateral sclerosis (ALS)-like features in motor neurons and improves lifespan in SOD1-ALS mice. Hum Mol Genet 17:2849–2862

    Article  PubMed  CAS  Google Scholar 

  38. Cote F, Collard JF, Julien JP (1993) Progressive neuronopathy in transgenic mice expressing the human neurofilament heavy gene: a mouse model of amyotrophic lateral sclerosis. Cell 73:35–46

    Article  PubMed  CAS  Google Scholar 

  39. Gama Sosa MA, Friedrich VL Jr, DeGasperi R, Kelley K, Wen PH, Senturk E, Lazzarini RA, Elder GA (2003) Human midsized neurofilament subunit induces motor neuron disease in transgenic mice. Exp Neurol 184:408–419

    Article  PubMed  CAS  Google Scholar 

  40. Xu Z, Cork LC, Griffin JW, Cleveland DW (1993) Increased expression of neurofilament subunit NF-L produces morphological alterations that resemble the pathology of human motor neuron disease. Cell 73:23–33

    Article  PubMed  CAS  Google Scholar 

  41. Meier J, Couillard-Despres S, Jacomy H, Gravel C, Julien JP (1999) Extra neurofilament NF-L subunits rescue motor neuron disease caused by overexpression of the human NF-H gene in mice. J Neuropathol Exp Neurol 58:1099–1110

    Article  PubMed  CAS  Google Scholar 

  42. Beaulieu JM, Nguyen MD, Julien JP (1999) Late onset of motor neurons in mice overexpressing wild-type peripherin. J Cell Biol 147:531–544

    Article  PubMed  CAS  Google Scholar 

  43. Beaulieu JM, Jacomy H, Julien JP (2000) Formation of intermediate filament protein aggregates with disparate effects in two transgenic mouse models lacking the neurofilament light subunit. J Neurosci 20:5321–5328

    PubMed  CAS  Google Scholar 

  44. Millecamps S, Robertson J, Lariviere R, Mallet J, Julien JP (2006) Defective axonal transport of neurofilament proteins in neurons overexpressing peripherin. J Neurochem 98:926–938

    Article  PubMed  CAS  Google Scholar 

  45. Perrot R, Julien JP (2009) Real-time imaging reveals defects of fast axonal transport induced by disorganization of intermediate filaments. Faseb J 23:3213–3225

    Article  PubMed  CAS  Google Scholar 

  46. Robertson J, Beaulieu JM, Doroudchi MM, Durham HD, Julien JP, Mushynski WE (2001) Apoptotic death of neurons exhibiting peripherin aggregates is mediated by the proinflammatory cytokine tumor necrosis factor-alpha. J Cell Biol 155:217–226

    Article  PubMed  CAS  Google Scholar 

  47. Beaulieu JM, Julien JP (2003) Peripherin-mediated death of motor neurons rescued by overexpression of neurofilament NF-H proteins. J Neurochem 85:248–256

    Article  PubMed  CAS  Google Scholar 

  48. Lariviere RC, Beaulieu JM, Nguyen MD, Julien JP (2003) Peripherin is not a contributing factor to motor neuron disease in a mouse model of amyotrophic lateral sclerosis caused by mutant superoxide dismutase. Neurobiol Dis 13:158–166

    Article  PubMed  CAS  Google Scholar 

  49. Bergeron C, Beric-Maskarel K, Muntasser S, Weyer L, Somerville MJ, Percy ME (1994) Neurofilament light and polyadenylated mRNA levels are decreased in amyotrophic lateral sclerosis motor neurons. J Neuropathol Exp Neurol 53:221–230

    Article  PubMed  CAS  Google Scholar 

  50. Strong MJ, Leystra-Lantz C, Ge WW (2004) Intermediate filament steady-state mRNA levels in amyotrophic lateral sclerosis. Biochem Biophys Res Commun 316:317–322

    Article  PubMed  CAS  Google Scholar 

  51. Wong NK, He BP, Strong MJ (2000) Characterization of neuronal intermediate filament protein expression in cervical spinal motor neurons in sporadic amyotrophic lateral sclerosis (ALS). J Neuropathol Exp Neurol 59:972–982

    PubMed  CAS  Google Scholar 

  52. Ge WW, Volkening K, Leystra-Lantz C, Jaffe H, Strong MJ (2007) 14-3-3 protein binds to the low molecular weight neurofilament (NFL) mRNA 3’ UTR. Mol Cell Neurosci 34:80–87

    Article  PubMed  CAS  Google Scholar 

  53. Strong MJ, Volkening K, Hammond R, Yang W, Strong W, Leystra-Lantz C, Shoesmith C (2007) TDP43 is a human low molecular weight neurofilament (hNFL) mRNA-binding protein. Mol Cell Neurosci 35:320–327

    Article  PubMed  CAS  Google Scholar 

  54. Ge WW, Wen W, Strong W, Leystra-Lantz C, Strong MJ (2005) Mutant copper-zinc superoxide dismutase binds to and destabilizes human low molecular weight neurofilament mRNA. J Biol Chem 280:118–124

    PubMed  CAS  Google Scholar 

  55. Volkening K, Leystra-Lantz C, Strong MJ (2010) Human low molecular weight neurofilament (NFL) mRNA interacts with a predicted p190RhoGEF homologue (RGNEF) in humans. Amyotroph Lateral Scler 11:97–103

    Article  PubMed  CAS  Google Scholar 

  56. Shan X, Chiang PM, Price DL, Wong PC (2010) Altered distributions of Gemini of coiled bodies and mitochondria in motor neurons of TDP-43 transgenic mice. Proc Natl Acad Sci U S A 107:16325–16330

    Article  PubMed  CAS  Google Scholar 

  57. Swarup V, Julien JP (2011) ALS pathogenesis: Recent insights from genetics and mouse models. Prog Neuropsychopharmacol Biol Psychiatry 35(2):363–369

    Article  PubMed  CAS  Google Scholar 

  58. Chou SM, Wang HS, Taniguchi A, Bucala R (1998) Advanced glycation endproducts in neurofilament conglomeration of motoneurons in familial and sporadic amyotrophic lateral sclerosis. Mol Med 4:324–332

    PubMed  CAS  Google Scholar 

  59. Crow JP, Ye YZ, Strong M, Kirk M, Barnes S, Beckman JS (1997) Superoxide dismutase catalyzes nitration of tyrosines by peroxynitrite in the rod and head domains of neurofilament-L. J Neurochem 69:1945–1953

    Article  PubMed  CAS  Google Scholar 

  60. Strong MJ, Sopper MM, Crow JP, Strong WL, Beckman JS (1998) Nitration of the low molecular weight neurofilament is equivalent in sporadic amyotrophic lateral sclerosis and control cervical spinal cord. Biochem Biophys Res Commun 248:157–164

    Article  PubMed  CAS  Google Scholar 

  61. King AE, Dickson TC, Blizzard CA, Woodhouse A, Foster SS, Chung RS, Vickers JC (2009) Neuron-glia interactions underlie ALS-like axonal cytoskeletal pathology. Neurobiol Aging (Epub)

    Google Scholar 

  62. Eyer J, Cleveland DW, Wong PC, Peterson AC (1998) Pathogenesis of two axonopathies does not require axonal neurofilaments. Nature 391:584–587

    Article  PubMed  CAS  Google Scholar 

  63. Williamson TL, Bruijn LI, Zhu Q, Anderson KL, Anderson SD, Julien JP, Cleveland DW (1998) Absence of neurofilaments reduces the selective vulnerability of motor neurons and slows disease caused by a familial amyotrophic lateral sclerosis-linked superoxide dismutase 1 mutant. Proc Natl Acad Sci U S A 95:9631–9636

    Article  PubMed  CAS  Google Scholar 

  64. Kong J, Xu Z (2000) Overexpression of neurofilament subunit NF-L and NF-H extends survival of a mouse model for amyotrophic lateral sclerosis. Neurosci Lett 281:72–74

    Article  PubMed  CAS  Google Scholar 

  65. Couillard-Despres S, Zhu Q, Wong PC, Price DL, Cleveland DW, Julien JP (1998) Protective effect of neurofilament heavy gene overexpression in motor neuron disease induced by mutant superoxide dismutase. Proc Natl Acad Sci U S A 95:9626–9630

    Article  PubMed  CAS  Google Scholar 

  66. Nguyen MD, Lariviere RC, Julien JP (2000) Reduction of axonal caliber does not alleviate motor neuron disease caused by mutant superoxide dismutase 1. Proc Natl Acad Sci U S A 97:12306–12311

    Article  PubMed  CAS  Google Scholar 

  67. Roy J, Minotti S, Dong L, Figlewicz DA, Durham HD (1998) Glutamate potentiates the toxicity of mutant Cu/Zn-superoxide dismutase in motor neurons by postsynaptic calcium-dependent mechanisms. J Neurosci 18:9673–9684

    PubMed  CAS  Google Scholar 

  68. Tu PH, Raju P, Robinson KA, Gurney ME, Trojanowski JQ, Lee VM (1996) Transgenic mice carrying a human mutant superoxide dismutase transgene develop neuronal cytoskeletal pathology resembling human amyotrophic lateral sclerosis lesions. Proc Natl Acad Sci U S A 93:3155–3160

    Article  PubMed  CAS  Google Scholar 

  69. Lobsiger CS, Garcia ML, Ward CM, Cleveland DW (2005) Altered axonal architecture by removal of the heavily phosphorylated neurofilament tail domains strongly slows superoxide dismutase 1 mutant-mediated ALS. Proc Natl Acad Sci U S A 102:10351–10356

    Article  PubMed  CAS  Google Scholar 

  70. Ehlers MD, Fung ET, O’Brien RJ, Huganir RL (1998) Splice variant-specific interaction of the NMDA receptor subunit NR1 with neuronal intermediate filaments. J Neurosci 18:720–730

    PubMed  CAS  Google Scholar 

  71. Sanelli T, Ge W, Leystra-Lantz C, Strong MJ (2007) Calcium mediated excitotoxicity in neurofilament aggregate-bearing neurons in vitro is NMDA receptor dependant. J Neurol Sci 256:39–51

    Article  PubMed  CAS  Google Scholar 

  72. Vogel P, Gabriel M, Goebel HH, Dyck PJ (1985) Hereditary motor sensory neuropathy type II with neurofilament accumulation: new finding or new disorder? Ann Neurol 17:455–461

    Article  PubMed  CAS  Google Scholar 

  73. Brownlees J, Ackerley S, Grierson AJ, Jacobsen NJ, Shea K, Anderton BH, Leigh PN, Shaw CE, Miller CC (2002) Charcot-Marie-Tooth disease neurofilament mutations disrupt neurofilament assembly and axonal transport. Hum Mol Genet 11:2837–2844

    Article  PubMed  CAS  Google Scholar 

  74. Perez-Olle R, Lopez-Toledano MA, Goryunov D, Cabrera-Poch N, Stefanis L, Brown K, Liem RK (2005) Mutations in the neurofilament light gene linked to Charcot-Marie-Tooth disease cause defects in transport. J Neurochem 93:861–874

    Article  PubMed  CAS  Google Scholar 

  75. Lee IB, Kim SK, Chung SH, Kim H, Kwon TK, Min do S, Chang JS (2008) The effect of rod domain A148V mutation of neurofilament light chain on filament formation. BMB Rep 41:868–874

    Article  PubMed  CAS  Google Scholar 

  76. Shin JS, Chung KW, Cho SY, Yun J, Hwang SJ, Kang SH, Cho EM, Kim SM, Choi BO (2008) NEFL Pro22Arg mutation in Charcot-Marie-Tooth disease type 1. J Hum Genet 53:936–940

    Article  PubMed  Google Scholar 

  77. Georgiou DM, Zidar J, Korosec M, Middleton LT, Kyriakides T, Christodoulou K (2002) A novel NF-L mutation Pro22Ser is associated with CMT2 in a large Slovenian family. Neurogenetics 4:93–96

    Article  PubMed  CAS  Google Scholar 

  78. Fabrizi GM, Cavallaro T, Angiari C, Bertolasi L, Cabrini I, Ferrarini M, Rizzuto N (2004) Giant axon and neurofilament accumulation in Charcot-Marie-Tooth disease type 2E. Neurology 62:1429–1431

    Article  PubMed  CAS  Google Scholar 

  79. Bhagavati S, Maccabee PJ, Xu W (2009) The neurofilament light chain gene (NEFL) mutation Pro22Ser can be associated with mixed axonal and demyelinating neuropathy. J Clin Neurosci 16:830–831

    Article  PubMed  CAS  Google Scholar 

  80. Yoshihara T, Yamamoto M, Hattori N, Misu K, Mori K, Koike H, Sobue G (2002) Identification of novel sequence variants in the neurofilament-light gene in a Japanese population: analysis of Charcot-Marie-Tooth disease patients and normal individuals. J Peripher Nerv Syst 7:221–224

    Article  PubMed  CAS  Google Scholar 

  81. Sasaki T, Gotow T, Shiozaki M, Sakaue F, Saito T, Julien JP, Uchiyama Y, Hisanaga S (2006) Aggregate formation and phosphorylation of neurofilament-L Pro22 Charcot-Marie-Tooth disease mutants. Hum Mol Genet 15:943–952

    Article  PubMed  CAS  Google Scholar 

  82. Jordanova A, De Jonghe P, Boerkoel CF, Takashima H, De Vriendt E, Ceuterick C, Martin JJ, Butler IJ, Mancias P, Papasozomenos S, Terespolsky D, Potocki L, Brown CW, Shy M, Rita DA, Tournev I, Kremensky I, Lupski JR, Timmerman V (2003) Mutations in the neurofilament light chain gene (NEFL) cause early onset severe Charcot-Marie-Tooth disease. Brain 126:590–597

    Article  PubMed  CAS  Google Scholar 

  83. Choi BO, Lee MS, Shin SH, Hwang JH, Choi KG, Kim WK, Sunwoo IN, Kim NK, Chung KW (2004) Mutational analysis of PMP22, MPZ, GJB1, EGR2 and NEFL in Korean Charcot-Marie-Tooth neuropathy patients. Hum Mutat 24:185–186

    Article  PubMed  CAS  Google Scholar 

  84. Zuchner S, Vorgerd M, Sindern E, Schroder JM (2004) The novel neurofilament light (NEFL) mutation Glu397Lys is associated with a clinically and morphologically heterogeneous type of Charcot-Marie-Tooth neuropathy. Neuromuscul Disord 14:147–157

    Article  PubMed  Google Scholar 

  85. Fabrizi GM, Cavallaro T, Angiari C, Cabrini I, Taioli F, Malerba G, Bertolasi L, Rizzuto N (2007) Charcot-Marie-Tooth disease type 2E, a disorder of the cytoskeleton. Brain 130:394–403

    Article  PubMed  Google Scholar 

  86. Leung CL, Nagan N, Graham TH, Liem RK (2006) A novel duplication/insertion mutation of NEFL in a patient with Charcot-Marie-Tooth disease. Am J Med Genet A 140:1021–1025

    PubMed  Google Scholar 

  87. Abe A, Numakura C, Saito K, Koide H, Oka N, Honma A, Kishikawa Y, Hayasaka K (2009) Neurofilament light chain polypeptide gene mutations in Charcot-Marie-Tooth disease: nonsense mutation probably causes a recessive phenotype. J Hum Genet 54:94–97

    Article  PubMed  CAS  Google Scholar 

  88. Dequen F, Filali M, Lariviere RC, Perrot R, Hisanaga S, Julien JP (2011) Reversal of neuropathy phenotypes in conditional mouse model of Charcot-Marie-Tooth disease type 2E. Hum Mol Genet 19:2616–2629

    Article  CAS  Google Scholar 

  89. Ackerley S, James PA, Kalli A, French S, Davies KE, Talbot K (2006) A mutation in the small heat-shock protein HSPB1 leading to distal hereditary motor neuronopathy disrupts neurofilament assembly and the axonal transport of specific cellular cargoes. Hum Mol Genet 15:347–354

    Article  PubMed  CAS  Google Scholar 

  90. Evgrafov OV, Mersiyanova I, Irobi J, Van Den Bosch L, Dierick I, Leung CL, Schagina O, Verpoorten N, Van Impe K, Fedotov V, Dadali E, Auer-Grumbach M, Windpassinger C, Wagner K, Mitrovic Z, Hilton-Jones D, Talbot K, Martin JJ, Vasserman N, Tverskaya S, Polyakov A, Liem RK, Gettemans J, Robberecht W, De Jonghe P, Timmerman V (2004) Mutant small heat-shock protein 27 causes axonal Charcot-Marie-Tooth disease and distal hereditary motor neuropathy. Nat Genet 36:602–606

    Article  PubMed  CAS  Google Scholar 

  91. Goryunov D, Nightingale A, Bornfleth L, Leung C, Liem RK (2008) Multiple disease-linked myotubularin mutations cause NFL assembly defects in cultured cells and disrupt myotubularin dimerization. J Neurochem 104:1536–1552

    Article  PubMed  CAS  Google Scholar 

  92. Irobi J, Van Impe K, Seeman P, Jordanova A, Dierick I, Verpoorten N, Michalik A, De Vriendt E, Jacobs A, Van Gerwen V, Vennekens K, Mazanec R, Tournev I, Hilton-Jones D, Talbot K, Kremensky I, Van Den Bosch L, Robberecht W, Van Vandekerckhove J, Van Broeckhoven C, Gettemans J, De Jonghe P, Timmerman V (2004) Hot-spot residue in small heat-shock protein 22 causes distal motor neuropathy. Nat Genet 36:597–601

    Article  PubMed  CAS  Google Scholar 

  93. Zhai J, Lin H, Julien JP, Schlaepfer WW (2007) Disruption of neurofilament network with aggregation of light neurofilament protein: a common pathway leading to motor neuron degeneration due to Charcot-Marie-Tooth disease-linked mutations in NFL and HSPB1. Hum Mol Genet 16:3103–3116

    Article  PubMed  CAS  Google Scholar 

  94. Tradewell ML, Durham HD, Mushynski WE, Gentil BJ (2009) Mitochondrial and axonal abnormalities precede disruption of the neurofilament network in a model of Charcot-Marie-Tooth disease type 2E and are prevented by heat shock proteins in a mutant-specific fashion. J Neuropathol Exp Neurol 68:642–652

    Article  PubMed  CAS  Google Scholar 

  95. Bomont P, Cavalier L, Blondeau F, Ben HC, Belal S, Tazir M, Demir E, Topaloglu H, Korinthenberg R, Tuysuz B, Landrieu P, Hentati F, Koenig M (2000) The gene encoding gigaxonin, a new member of the cytoskeletal BTB/kelch repeat family, is mutated in giant axonal neuropathy. Nat Genet 26:370–374

    Article  PubMed  CAS  Google Scholar 

  96. Peiffer J, Schlote W, Bischoff A, Boltshauser E, Muller G (1977) Generalized giant axonal neuropathy: a filament-forming disease of neuronal, endothelial, glial, and schwann cells in a patient without kinky hair. Acta Neuropathol 40:213–218

    Article  PubMed  CAS  Google Scholar 

  97. Asbury AK, Gale MK, Cox SC, Baringer JR, Berg BO (1972) Giant axonal neuropathy—a unique case with segmental neurofilamentous masses. Acta Neuropathol 20:237–247

    Article  PubMed  CAS  Google Scholar 

  98. Fois A, Balestri P, Farnetani MA, Berardi R, Mattei R, Laurenzi E, Alessandrini C, Gerli R, Ribuffo A, Calvieri S (1985) Giant axonal neuropathy. Endocrinological and histological studies. Eur J Pediatr 144:274–280

    Article  PubMed  CAS  Google Scholar 

  99. Mohri I, Taniike M, Yoshikawa H, Higashiyama M, Itami S, Okada S (1998) A case of giant axonal neuropathy showing focal aggregation and hypophosphorylation of intermediate filaments. Brain Dev 20:594–597

    Article  PubMed  CAS  Google Scholar 

  100. Treiber-Held S, Budjarjo-Welim H, Reimann D, Richter J, Kretzschmar HA, Hanefeld F (1994) Giant axonal neuropathy: a generalized disorder of intermediate filaments with longitudinal grooves in the hair. Neuropediatrics 25:89–93

    Article  PubMed  CAS  Google Scholar 

  101. Donaghy M, King RH, Thomas PK, Workman JM (1988) Abnormalities of the axonal cytoskeleton in giant axonal neuropathy. J Neurocytol 17:197–208

    Article  PubMed  CAS  Google Scholar 

  102. Monaco S, Autilio-Gambetti L, Zabel D, Gambetti P (1985) Giant axonal neuropathy: acceleration of neurofilament transport in optic axons. Proc Natl Acad Sci U S A 82:920–924

    Article  PubMed  CAS  Google Scholar 

  103. Ding J, Allen E, Wang W, Valle A, Wu C, Nardine T, Cui B, Yi J, Taylor A, Jeon NL, Chu S, So Y, Vogel H, Tolwani R, Mobley W, Yang Y (2006) Gene targeting of GAN in mouse causes a toxic accumulation of microtubule-associated protein 8 and impaired retrograde axonal transport. Hum Mol Genet 15:1451–1463

    Article  PubMed  CAS  Google Scholar 

  104. Yang Y, Allen E, Ding J, Wang W (2007) Giant axonal neuropathy. Cell Mol Life Sci 64:601–609

    Article  PubMed  CAS  Google Scholar 

  105. Dequen F, Bomont P, Gowing G, Cleveland DW, Julien JP (2008) Modest loss of peripheral axons, muscle atrophy and formation of brain inclusions in mice with targeted deletion of gigaxonin exon 1. J Neurochem 107:253–264

    Article  PubMed  CAS  Google Scholar 

  106. Ding J, Liu JJ, Kowal AS, Nardine T, Bhattacharya P, Lee A, Yang Y (2002) Microtubule-associated protein 1B: a neuronal binding partner for gigaxonin. J Cell Biol 158:427–433

    Article  PubMed  CAS  Google Scholar 

  107. Wang W, Ding J, Allen E, Zhu P, Zhang L, Vogel H, Yang Y (2005) Gigaxonin interacts with tubulin folding cofactor B and controls its degradation through the ubiquitin-proteasome pathway. Curr Biol 15:2050–2055

    Article  PubMed  CAS  Google Scholar 

  108. Allen E, Ding J, Wang W, Pramanik S, Chou J, Yau V, Yang Y (2005) Gigaxonin-controlled degradation of MAP1B light chain is critical to neuronal survival. Nature 438:224–228

    Article  PubMed  CAS  Google Scholar 

  109. Cleveland DW, Yamanaka K, Bomont P (2009) Gigaxonin controls vimentin organization through a tubulin chaperone-independent pathway. Hum Mol Genet 18:1384–1394

    Article  PubMed  CAS  Google Scholar 

  110. Cairns NJ, Zhukareva V, Uryu K, Zhang B, Bigio E, Mackenzie IR, Gearing M, Duyckaerts C, Yokoo H, Nakazato Y, Jaros E, Perry RH, Lee VM, Trojanowski JQ (2004) alpha-internexin is present in the pathological inclusions of neuronal intermediate filament inclusion disease. Am J Pathol 164:2153–2161

    Article  PubMed  CAS  Google Scholar 

  111. Uchikado H, Shaw G, Wang DS, Dickson DW (2005) Screening for neurofilament inclusion disease using alpha-internexin immunohistochemistry. Neurology 64:1658–1659

    Article  PubMed  Google Scholar 

  112. Momeni P, Cairns NJ, Perry RH, Bigio EH, Gearing M, Singleton AB, Hardy J (2006) Mutation analysis of patients with neuronal intermediate filament inclusion disease (NIFID). Neurobiol Aging 27:778 e1–778 e6

    Article  PubMed  CAS  Google Scholar 

  113. Dequen F, Cairns NJ, Bigio EH, Julien JP (2009) Gigaxonin mutation analysis in patients with NIFID. Neurobiol Aging (Epub)

    Google Scholar 

  114. Neumann M, Roeber S, Kretzschmar HA, Rademakers R, Baker M, Mackenzie IR (2009) Abundant FUS-immunoreactive pathology in neuronal intermediate filament inclusion disease. Acta Neuropathol 118:605–616

    Article  PubMed  CAS  Google Scholar 

  115. Medori R, Autilio-Gambetti L, Monaco S, Gambetti P (1985) Experimental diabetic neuropathy: impairment of slow transport with changes in axon cross-sectional area. Proc Natl Acad Sci U S A 82:7716–7720

    Article  PubMed  CAS  Google Scholar 

  116. Medori R, Jenich H, Autilio-Gambetti L, Gambetti P (1988) Experimental diabetic neuropathy: similar changes of slow axonal transport and axonal size in different animal models. J Neurosci 8:1814–1821

    PubMed  CAS  Google Scholar 

  117. Yagihashi S, Kamijo M, Watanabe K (1990) Reduced myelinated fiber size correlates with loss of axonal neurofilaments in peripheral nerve of chronically streptozotocin diabetic rats. Am J Pathol 136:1365–1373

    PubMed  CAS  Google Scholar 

  118. Schmidt RE, Beaudet LN, Plurad SB, Dorsey DA (1997) Axonal cytoskeletal pathology in aged and diabetic human sympathetic autonomic ganglia. Brain Res 769:375–383

    Article  PubMed  CAS  Google Scholar 

  119. Fernyhough P, Gallagher A, Averill SA, Priestley JV, Hounsom L, Patel J, Tomlinson DR (1999) Aberrant neurofilament phosphorylation in sensory neurons of rats with diabetic neuropathy. Diabetes 48:881–889

    Article  PubMed  CAS  Google Scholar 

  120. Scott JN, Clark AW, Zochodne DW (1999) Neurofilament and tubulin gene expression in progressive experimental diabetes: failure of synthesis and export by sensory neurons. Brain 122 (Pt 11):2109–2118

    Article  PubMed  Google Scholar 

  121. Zochodne DW, Sun HS, Cheng C, Eyer J (2004) Accelerated diabetic neuropathy in axons without neurofilaments. Brain 127:2193–2200

    Article  PubMed  Google Scholar 

  122. Forno LS, Sternberger LA, Sternberger NH, Strefling AM, Swanson K, Eng LF (1986) Reaction of Lewy bodies with antibodies to phosphorylated and non-phosphorylated neurofilaments. Neurosci Lett 64:253–258

    Article  PubMed  CAS  Google Scholar 

  123. Pappolla MA (1986) Lewy bodies of Parkinson’s disease. Immune electron microscopic demonstration of neurofilament antigens in constituent filaments. Arch Pathol Lab Med 110:1160–1163

    PubMed  CAS  Google Scholar 

  124. Hill WD, Arai M, Cohen JA, Trojanowski JQ (1993) Neurofilament mRNA is reduced in Parkinson’s disease substantia nigra pars compacta neurons. J Comp Neurol 329:328–336

    Article  PubMed  CAS  Google Scholar 

  125. Lavedan C, Buchholtz S, Nussbaum RL, Albin RL, Polymeropoulos MH (2002) A mutation in the human neurofilament M gene in Parkinson’s disease that suggests a role for the cytoskeleton in neuronal degeneration. Neurosci Lett 322:57–61

    Article  PubMed  CAS  Google Scholar 

  126. Perez-Olle R, Lopez-Toledano MA, Liem RK (2004) The G336S variant in the human neurofilament-M gene does not affect its assembly or distribution: importance of the functional analysis of neurofilament variants. J Neuropathol Exp Neurol 63:759–774

    PubMed  CAS  Google Scholar 

  127. Han F, Bulman DE, Panisset M, Grimes DA (2005) Neurofilament M gene in a French-Canadian population with Parkinson’s disease. Can J Neurol Sci 32:68–70

    PubMed  CAS  Google Scholar 

  128. Kruger R, Fischer C, Schulte T, Strauss KM, Muller T, Woitalla D, Berg D, Hungs M, Gobbele R, Berger K, Epplen JT, Riess O, Schols L (2003) Mutation analysis of the neurofilament M gene in Parkinson’s disease. Neurosci Lett 351:125–129

    Article  PubMed  CAS  Google Scholar 

  129. Liem RK, Messing A (2009) Dysfunctions of neuronal and glial intermediate filaments in disease. J Clin Invest 119:1814–1824

    Article  PubMed  CAS  Google Scholar 

  130. Sawaishi Y (2009) Review of Alexander disease: beyond the classical concept of leukodystrophy. Brain Dev 31:493–498

    Article  PubMed  Google Scholar 

  131. Bettica A, Johnson AB (1990) Ultrastructural immunogold labeling of glial filaments in osmicated and unosmicated epoxy-embedded tissue. J Histochem Cytochem 38:103–109

    Article  PubMed  CAS  Google Scholar 

  132. Tomokane N, Iwaki T, Tateishi J, Iwaki A, Goldman JE (1991) Rosenthal fibers share epitopes with alpha B-crystallin, glial fibrillary acidic protein, and ubiquitin, but not with vimentin. Immunoelectron microscopy with colloidal gold. Am J Pathol 138:875–885

    PubMed  CAS  Google Scholar 

  133. Head MW, Corbin E, Goldman JE (1993) Overexpression and abnormal modification of the stress proteins alpha B-crystallin and HSP27 in Alexander disease. Am J Pathol 143:1743–1753

    PubMed  CAS  Google Scholar 

  134. Gomi H, Yokoyama T, Fujimoto K, Ikeda T, Katoh A, Itoh T, Itohara S (1995) Mice devoid of the glial fibrillary acidic protein develop normally and are susceptible to scrapie prions. Neuron 14:29–41

    Article  PubMed  CAS  Google Scholar 

  135. Pekny M, Leveen P, Pekna M, Eliasson C, Berthold CH, Westermark B, Betsholtz C (1995) Mice lacking glial fibrillary acidic protein display astrocytes devoid of intermediate filaments but develop and reproduce normally. Embo J 14:1590–1598

    PubMed  CAS  Google Scholar 

  136. Liedtke W, Edelmann W, Bieri PL, Chiu FC, Cowan NJ, Kucherlapati R, Raine CS (1996) GFAP is necessary for the integrity of CNS white matter architecture and long-term maintenance of myelination. Neuron 17:607–615

    Article  PubMed  CAS  Google Scholar 

  137. McCall MA, Gregg RG, Behringer RR, Brenner M, Delaney CL, Galbreath EJ, Zhang CL, Pearce RA, Chiu SY, Messing A (1996) Targeted deletion in astrocyte intermediate filament (Gfap) alters neuronal physiology. Proc Natl Acad Sci U S A 93:6361–6366

    Article  PubMed  CAS  Google Scholar 

  138. Messing A, Head MW, Galles K, Galbreath EJ, Goldman JE, Brenner M (1998) Fatal encephalopathy with astrocyte inclusions in GFAP transgenic mice. Am J Pathol 152:391–398

    PubMed  CAS  Google Scholar 

  139. Hagemann TL, Gaeta SA, Smith MA, Johnson DA, Johnson JA, Messing A (2005) Gene expression analysis in mice with elevated glial fibrillary acidic protein and Rosenthal fibers reveals a stress response followed by glial activation and neuronal dysfunction. Hum Mol Genet 14:2443–2458

    Article  PubMed  CAS  Google Scholar 

  140. Brenner M, Johnson AB, Boespflug-Tanguy O, Rodriguez D, Goldman JE, Messing A (2001) Mutations in GFAP, encoding glial fibrillary acidic protein, are associated with Alexander disease. Nat Genet 27:117–120

    Article  PubMed  CAS  Google Scholar 

  141. McClintock KA, Shaw GS (2000) A logical sequence search for S100B target proteins. Protein Sci 9:2043–2046

    Article  PubMed  CAS  Google Scholar 

  142. Donato R (1999) Functional roles of S100 proteins, calcium-binding proteins of the EF-hand type. Biochim Biophys Acta 1450:191–231

    Article  PubMed  CAS  Google Scholar 

  143. Li R, Johnson AB, Salomons G, Goldman JE, Naidu S, Quinlan R, Cree B, Ruyle SZ, Banwell B, D’Hooghe M, Siebert JR, Rolf CM, Cox H, Reddy A, Gutierrez-Solana LG, Collins A, Weller RO, Messing A, Van Der Knaap MS, Brenner M (2005) Glial fibrillary acidic protein mutations in infantile, juvenile, and adult forms of Alexander disease. Ann Neurol 57:310–326

    Article  PubMed  CAS  Google Scholar 

  144. Gorospe JR, Naidu S, Johnson AB, Puri V, Raymond GV, Jenkins SD, Pedersen RC, Lewis D, Knowles P, Fernandez R, De Vivo D, Van Der Knaap MS, Messing A, Brenner M, Hoffman EP (2002) Molecular findings in symptomatic and pre-symptomatic Alexander disease patients. Neurology 58:1494–1500

    Article  PubMed  CAS  Google Scholar 

  145. Hagemann TL, Connor JX, Messing A (2006) Alexander disease-associated glial fibrillary acidic protein mutations in mice induce Rosenthal fiber formation and a white matter stress response. J Neurosci 26:11162–11173

    Article  PubMed  CAS  Google Scholar 

  146. Tanaka KF, Takebayashi H, Yamazaki Y, Ono K, Naruse M, Iwasato T, Itohara S, Kato H, Ikenaka K (2007) Murine model of Alexander disease: analysis of GFAP aggregate formation and its pathological significance. Glia 55:617–631

    Article  PubMed  Google Scholar 

  147. Hsiao VC, Tian R, Long H, Der Perng M, Brenner M, Quinlan RA, Goldman JE (2005) Alexander-disease mutation of GFAP causes filament disorganization and decreased solubility of GFAP. J Cell Sci 118:2057–2065

    Article  PubMed  CAS  Google Scholar 

  148. Tang G, Xu Z, Goldman JE (2006) Synergistic effects of the SAPK/JNK and the proteasome pathway on glial fibrillary acidic protein (GFAP) accumulation in Alexander disease. J Biol Chem 281:38634–38643

    Article  PubMed  CAS  Google Scholar 

  149. Tian R, Gregor M, Wiche G, Goldman JE (2006) Plectin regulates the organization of glial fibrillary acidic protein in Alexander disease. Am J Pathol 168:888–897

    Article  PubMed  CAS  Google Scholar 

  150. Iwaki T, Kume-Iwaki A, Liem RK, Goldman JE (1989) Alpha B-crystallin is expressed in non-lenticular tissues and accumulates in Alexander’s disease brain. Cell 57:71–78

    Article  PubMed  CAS  Google Scholar 

  151. Koyama Y, Goldman JE (1999) Formation of GFAP cytoplasmic inclusions in astrocytes and their disaggregation by alphaB-crystallin. Am J Pathol 154:1563–1572

    Article  PubMed  CAS  Google Scholar 

  152. Tang G, Yue Z, Talloczy Z, Hagemann T, Cho W, Messing A, Sulzer DL, Goldman JE (2008) Autophagy induced by Alexander disease-mutant GFAP accumulation is regulated by p38/MAPK and mTOR signaling pathways. Hum Mol Genet 17:1540–1555

    Article  PubMed  CAS  Google Scholar 

  153. Bachetti T, Di Zanni E, Balbi P, Bocca P, Prigione I, Deiana GA, Rezzani A, Ceccherini I, Sechi G (2010) In vitro treatments with ceftriaxone promote elimination of mutant glial fibrillary acidic protein and transcription down-regulation. Exp Cell Res 316:2152–2165

    Article  PubMed  CAS  Google Scholar 

  154. Perng MD, Wen SF, Gibbon T, Middeldorp J, Sluijs J, Hol EM, Quinlan RA (2008) Glial fibrillary acidic protein filaments can tolerate the incorporation of assembly-compromised GFAP-delta, but with consequences for filament organization and alphaB-crystallin association. Mol Biol Cell 19:4521–4533

    Article  PubMed  CAS  Google Scholar 

  155. Sunesson L, Hellman U, Larsson C (2008) Protein kinase Cepsilon binds peripherin and induces its aggregation, which is accompanied by apoptosis of neuroblastoma cells. J Biol Chem 283:16653–16664

    Article  PubMed  CAS  Google Scholar 

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  1. Service Commun d’Imageries et d’Analyses Microscopiques Institut de Biologie en Santé, Angers University, CHU, 4 Rue Larrey, 49933, ANGERS Cedex 09, France

    Rodolphe Perrot & Jean-Pierre Julien

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    Maria Kavallaris

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Perrot, R., Julien, JP. (2012). Neurodegenerative Diseases and Intermediate Filaments. In: Kavallaris, M. (eds) Cytoskeleton and Human Disease. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-788-0_20

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