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Pathologies of axonal transport in neurodegenerative diseases

  • Review Article
  • Published:
Translational Neuroscience

Abstract

Gene products such as organelles, proteins and RNAs are actively transported to synaptic terminals for the remodeling of pre-existing neuronal connections and formation of new ones. Proteins described as molecular motors mediate this transport and utilize specialized cytoskeletal proteins that function as molecular tracks for the motor based transport of cargos. Molecular motors such as kinesins and dynein’s move along microtubule tracks formed by tubulins whereas myosin motors utilize tracks formed by actin. Deficits in active transport of gene products have been implicated in a number of neurological disorders. We describe such disorders collectively as “transportopathies”. Here we review current knowledge of critical components of active transport and their relevance to neurodegenerative diseases.

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References

  1. Hirokawa N., Niwa S., Tanaka Y., Molecular motors in neurons: transport mechanisms and roles in brain function, development, and disease, Neuron, 2010, 68, 610–638

    Article  PubMed  CAS  Google Scholar 

  2. Chao M. V., Retrograde transport redux, Neuron, 2003, 39, 1–2

    Article  PubMed  CAS  Google Scholar 

  3. Ikenaka K., Katsuno M., Kawai K., Ishigaki S., Tanaka F., Sobue G., Disruption of axonal transport in motor neuron diseases, Int. J. Mol. Sci., 2012, 13, 1225–1238

    Article  PubMed  CAS  Google Scholar 

  4. Hollenbeck P. J., Saxton W. M., The axonal transport of mitochondria, J. Cell Sci., 2005, 118, 5411–5419

    Article  PubMed  CAS  Google Scholar 

  5. Caviston J. P., Holzbaur E. L., Microtubule motors at the intersection of trafficking and transport, Trends Cell Biol., 2006, 16, 530–537

    Article  PubMed  CAS  Google Scholar 

  6. Hirokawa N., Takemura R., Molecular motors and mechanisms of directional transport in neurons, Nat. Rev. Neurosci., 2005, 6, 201–214

    Article  PubMed  CAS  Google Scholar 

  7. Verhey K. J., Rapoport T. A., Kinesin carries the signal, Trends Biochem. Sci., 2001, 26, 545–550

    Article  PubMed  CAS  Google Scholar 

  8. Gunawardena S., Goldstein L. S., Cargo-carrying motor vehicles on the neuronal highway: transport pathways and neurodegenerative disease, J. Neurobiol., 2004, 58, 258–271

    Article  PubMed  CAS  Google Scholar 

  9. Kardon J. R., Vale R. D., Regulators of the cytoplasmic dynein motor, Nat. Rev. Mol. Cell. Biol., 2009, 10, 854–865

    Article  PubMed  CAS  Google Scholar 

  10. Kapitein L. C., Hoogenraad C. C., Which way to go? Cytoskeletal organization and polarized transport in neurons, Mol. Cell. Neurosci., 2011, 46, 9–20

    Article  PubMed  CAS  Google Scholar 

  11. Conde C., Caceres A., Microtubule assembly, organization and dynamics in axons and dendrites, Nat. Rev. Neurosci., 2009, 10, 319–332

    Article  PubMed  CAS  Google Scholar 

  12. Signor D., Scholey J. M., Microtubule-based transport along axons, dendrites and axonemes, Essays Biochem., 2000, 35, 89–102

    PubMed  CAS  Google Scholar 

  13. Black M. M., Baas P. W., The basis of polarity in neurons, Trends Neurosci., 1989, 12, 211–214

    Article  PubMed  CAS  Google Scholar 

  14. Zheng Y., Wong M. L., Alberts B., Mitchison T., Nucleation of microtubule assembly by a gamma-tubulin-containing ring complex, Nature, 1995, 378, 578–583

    Article  PubMed  CAS  Google Scholar 

  15. Schuyler S. C., Pellman D., Microtubule “plus-end-tracking proteins”: The end is just the beginning, Cell, 2001, 105, 421–424

    Article  PubMed  CAS  Google Scholar 

  16. Galjart N., Plus-end-tracking proteins and their interactions at microtubule ends, Curr. Biol., 2010, 20, R528–537

    Article  PubMed  CAS  Google Scholar 

  17. Dehmelt L., Halpain S., The MAP2/Tau family of microtubuleassociated proteins, Genome Biol., 2005, 6, 204

    Article  PubMed  Google Scholar 

  18. Halpain S., Dehmelt L., The MAP1 family of microtubule-associated proteins, Genome Biol., 2006, 7, 224

    Article  PubMed  CAS  Google Scholar 

  19. Caceres A., Kosik K. S., Inhibition of neurite polarity by tau antisense oligonucleotides in primary cerebellar neurons, Nature, 1990, 343, 461–463

    Article  PubMed  CAS  Google Scholar 

  20. Caceres A., Mautino J., Kosik K. S., Suppression of MAP2 in cultured cerebellar macroneurons inhibits minor neurite formation, Neuron, 1992, 9, 607–618

    Article  PubMed  CAS  Google Scholar 

  21. Harada A., Oguchi K., Okabe S., Kuno J., Terada S., Ohshima T., et al., Altered microtubule organization in small-calibre axons of mice lacking tau protein, Nature, 1994, 369, 488–491

    Article  PubMed  CAS  Google Scholar 

  22. Hirokawa N., Kinesin and dynein superfamily proteins and the mechanism of organelle transport, Science, 1998, 279, 519–526

    Article  PubMed  CAS  Google Scholar 

  23. Brady S. T., A novel brain ATPase with properties expected for the fast axonal transport motor, Nature, 1985, 317, 73–75

    Article  PubMed  CAS  Google Scholar 

  24. Vale R. D., Reese T. S., Sheetz M. P., Identification of a novel forcegenerating protein, kinesin, involved in microtubule-based motility, Cell, 1985, 42, 39–50

    Article  PubMed  CAS  Google Scholar 

  25. Aizawa H., Sekine Y., Takemura R., Zhang Z., Nangaku M., Hirokawa N., Kinesin family in murine central nervous system, J. Cell Biol., 1992, 119, 1287–1296

    Article  PubMed  CAS  Google Scholar 

  26. Lawrence C. J., Dawe R. K., Christie K. R., Cleveland D. W., Dawson S. C., Endow S. A., et al., A standardized kinesin nomenclature, J. Cell Biol., 2004, 167, 19–22

    Article  PubMed  CAS  Google Scholar 

  27. Brady S. T., Molecular motors in the nervous system, Neuron, 1991, 7, 521–533

    Article  PubMed  CAS  Google Scholar 

  28. Goldstein L. S., Yang Z., Microtubule-based transport systems in neurons: the roles of kinesins and dyneins, Annu. Rev. Neurosci., 2000, 23, 39–71

    Article  PubMed  CAS  Google Scholar 

  29. Goldstein L. S., Molecular motors: from one motor many tails to one motor many tales, Trends Cell Biol., 2001, 11, 477–482

    Article  PubMed  CAS  Google Scholar 

  30. Goldstein L. S., Kinesin molecular motors: transport pathways, receptors, and human disease, Proc. Natl. Acad. Sci. USA, 2001, 98, 6999–7003

    Article  PubMed  CAS  Google Scholar 

  31. Hirokawa N., mRNA transport in dendrites: RNA granules, motors, and tracks, J. Neurosci., 2006, 26, 7139–7142

    Article  PubMed  CAS  Google Scholar 

  32. Goldstein A. Y., Wang X., Schwarz T. L., Axonal transport and the delivery of pre-synaptic components, Curr. Opin. Neurobiol., 2008, 18, 495–503

    Article  PubMed  CAS  Google Scholar 

  33. Puthanveettil S. V., Monje F. J., Miniaci M. C., Choi Y. B., Karl K. A., Khandros E., et al., A new component in synaptic plasticity: upregulation of kinesin in the neurons of the gill-withdrawal reflex, Cell, 2008, 135, 960–973

    Article  PubMed  CAS  Google Scholar 

  34. Gibbons I. R., Rowe A. J., Dynein: a protein with adenosine triphosphatase activity from cilia, Science, 1965, 149, 424–426

    Article  PubMed  CAS  Google Scholar 

  35. Burns R. G., Pollard T. D., A dynein-like protein from brain, FEBS Lett., 1974, 40, 274–280

    Article  PubMed  CAS  Google Scholar 

  36. Vallee R. B., Shpetner H. S., Paschal B. M., The role of dynein in retrograde axonal transport, Trends Neurosci., 1989, 12, 66–70

    Article  PubMed  CAS  Google Scholar 

  37. Vale R. D., The molecular motor toolbox for intracellular transport, Cell, 2003, 112, 467–480

    Article  PubMed  CAS  Google Scholar 

  38. McGrath J. L., Dynein motility: four heads are better than two, Curr. Biol., 2005, 15, R970–972

    Article  PubMed  CAS  Google Scholar 

  39. King S. J., Schroer T. A., Dynactin increases the processivity of the cytoplasmic dynein motor, Nat. Cell Biol., 2000, 2, 20–24

    Article  PubMed  CAS  Google Scholar 

  40. Susalka S. J., Pfister K. K., Cytoplasmic dynein subunit heterogeneity: implications for axonal transport, J. Neurocytol., 2000, 29, 819–829

    Article  PubMed  CAS  Google Scholar 

  41. Vallee R. B., Williams J. C., Varma D., Barnhart L. E., Dynein: An ancient motor protein involved in multiple modes of transport, J. Neurobiol., 2004, 58, 189–200

    Article  PubMed  CAS  Google Scholar 

  42. Fifkova E., Delay R. J., Cytoplasmic actin in neuronal processes as a possible mediator of synaptic plasticity, J. Cell Biol., 1982, 95, 345–350

    Article  PubMed  CAS  Google Scholar 

  43. Luo L., Actin cytoskeleton regulation in neuronal morphogenesis and structural plasticity, Annu. Rev. Cell. Dev. Biol., 2002, 18, 601–635

    Article  PubMed  CAS  Google Scholar 

  44. Hotulainen P., Hoogenraad C. C., Actin in dendritic spines: connecting dynamics to function, J. Cell Biol., 2010, 189, 619–629

    Article  PubMed  CAS  Google Scholar 

  45. dos Remedios C. G., Chhabra D., Kekic M., Dedova I. V., Tsubakihara M., Berry D. A., et al., Actin binding proteins: regulation of cytoskeletal microfilaments, Physiol. Rev., 2003, 83, 433–473

    PubMed  Google Scholar 

  46. Puszkin S., Berl S., Puszkin E., Clarke D. D., Actomyosin-like protein isolated from mammalian brain, Science, 1968, 161, 170–171

    Article  PubMed  CAS  Google Scholar 

  47. Puszkin S., Nicklas W. J., Berl S., Actomyosin-like protein in brain: subcellular distribution, J. Neurochem., 1972, 19, 1319–1333

    Article  PubMed  CAS  Google Scholar 

  48. Bridgman P. C., Myosin-dependent transport in neurons, J. Neurobiol., 2004, 58, 164–174

    Article  PubMed  CAS  Google Scholar 

  49. Bridgman P.C., Elkin L. L., Axonal myosins, J. Neurocytol., 2000, 29, 831–841

    Article  PubMed  CAS  Google Scholar 

  50. Sellers J. R., Myosins: a diverse superfamily, Biochim. Biophys. Acta, 2000, 1496, 3–22

    Article  PubMed  CAS  Google Scholar 

  51. Titus M. A., Myosins, Curr. Opin. Cell Biol., 1993, 5, 77–81

    Article  PubMed  CAS  Google Scholar 

  52. Foth B. J., Goedecke M. C., Soldati D., New insights into myosin evolution and classification, Proc. Natl. Acad. Sci. USA, 2006, 103, 3681–3686

    Article  PubMed  CAS  Google Scholar 

  53. Dunn B. D., Sakamoto T., Hong M. S., Sellers J. R., Takizawa P. A., Myo4p is a monomeric myosin with motility uniquely adapted to transport mRNA, J. Cell Biol., 2007, 178, 1193–1206

    Article  PubMed  CAS  Google Scholar 

  54. Harrington W. F., Burke M., Geometry of the myosin dimer in highsalt media. I. Association behavior of rod segments from myosin, Biochemistry, 1972, 11, 1448–1455

    Article  PubMed  CAS  Google Scholar 

  55. Saitoh T., Takemura S., Ueda K., Hosoya H., Nagayama M., Haga H., et al., Differential localization of non-muscle myosin II isoforms and phosphorylated regulatory light chains in human MRC-5 fibroblasts, FEBS Lett., 2001, 509, 365–369

    Article  PubMed  CAS  Google Scholar 

  56. Vibert P., Cohen C., Domains, motions and regulation in the myosin head, J. Muscle Res. Cell. Motil., 1988, 9, 296–305

    Article  PubMed  CAS  Google Scholar 

  57. Krendel M., Mooseker M.S., Myosins: tails (and heads) of functional diversity, Physiology (Bethesda), 2005, 20, 239–251

    Article  CAS  Google Scholar 

  58. Syamaladevi D. P., Spudich J. A., Sowdhamini R., Structural and functional insights on the Myosin superfamily, Bioinform. Biol. Insights, 2012, 6, 11–21

    PubMed  CAS  Google Scholar 

  59. Wang Z., Edwards J. G., Riley N., Provance D. W. Jr., Karcher R., Li X. D., et al., Myosin Vb mobilizes recycling endosomes and AMPA receptors for postsynaptic plasticity, Cell, 2008, 135, 535–548

    Article  PubMed  CAS  Google Scholar 

  60. Wagner W., Brenowitz S. D., Hammer J. A. 3rd, Myosin-Va transports the endoplasmic reticulum into the dendritic spines of Purkinje neurons, Nat. Cell Biol., 2011, 13, 40–48

    Article  PubMed  CAS  Google Scholar 

  61. Phichith D., Travaglia M., Yang Z., Liu X., Zong A. B., Safer D., et al., Cargo binding induces dimerization of myosin VI, Proc. Natl. Acad. Sci. USA, 2009, 106, 17320–17324

    Article  PubMed  CAS  Google Scholar 

  62. Seabrooke S., Qiu X., Stewart B. A., Nonmuscle Myosin II helps regulate synaptic vesicle mobility at the Drosophila neuromuscular junction, BMC Neurosci., 2010, 11, 37

    Article  PubMed  CAS  Google Scholar 

  63. Gavin C. F., Rubio M. D., Young E., Miller C., Rumbaugh G., Myosin II motor activity in the lateral amygdala is required for fear memory consolidation, Learn. Mem., 2011, 19, 9–14

    Article  PubMed  CAS  Google Scholar 

  64. Rex C. S., Gavin C. F., Rubio M. D., Kramar E. A., Chen L. Y., Jia Y., et al., Myosin IIb regulates actin dynamics during synaptic plasticity and memory formation, Neuron, 2010, 67, 603–617

    Article  PubMed  CAS  Google Scholar 

  65. Hu X., Viesselmann C., Nam S., Merriam E., Dent E. W., Activitydependent dynamic microtubule invasion of dendritic spines, J. Neurosci., 2008, 28, 13094–13105

    Article  PubMed  CAS  Google Scholar 

  66. Maas C., Belgardt D., Lee H. K., Heisler F. F., Lappe-Siefke C., Magiera M. M., et al., Synaptic activation modifies microtubules underlying transport of postsynaptic cargo, Proc. Natl. Acad. Sci. USA, 2009, 106, 8731–8736

    Article  PubMed  CAS  Google Scholar 

  67. Hoogenraad C. C., Bradke F., Control of neuronal polarity and plasticity—a renaissance for microtubules?, Trends Cell Biol., 2009, 19, 669–676

    Article  PubMed  CAS  Google Scholar 

  68. Holzbaur E. L., Scherer S. S., Microtubules, axonal transport, and neuropathy, N. Engl. J. Med., 2011, 365, 2330–2332

    Article  PubMed  CAS  Google Scholar 

  69. Cambray-Deakin M. A., Burgoyne R. D., Posttranslational modifications of alpha-tubulin: acetylated and detyrosinated forms in axons of rat cerebellum, J. Cell Biol., 1987, 104, 1569–1574

    Article  PubMed  CAS  Google Scholar 

  70. Audebert S., Koulakoff A., Berwald-Netter Y., Gros F., Denoulet P., Edde B., Developmental regulation of polyglutamylated alpha- and betatubulin in mouse brain neurons, J. Cell Sci., 1994, 107, 2313–2322

    PubMed  CAS  Google Scholar 

  71. Mansfield S. G., Gordon-Weeks P. R., Dynamic post-translational modification of tubulin in rat cerebral cortical neurons extending neurites in culture: effects of taxol, J. Neurocytol., 1991, 20, 654–666

    Article  PubMed  CAS  Google Scholar 

  72. Billingsley M. L., Kincaid R. L., Regulated phosphorylation and dephosphorylation of tau protein: effects on microtubule interaction, intracellular trafficking and neurodegeneration, Biochem. J., 1997, 323, 577–591

    PubMed  CAS  Google Scholar 

  73. Perdiz D., Mackeh R., Pous C., Baillet A., The ins and outs of tubulin acetylation: more than just a post-translational modification?, Cell. Signal., 2011, 23, 763–771

    Article  PubMed  CAS  Google Scholar 

  74. Janke C., Kneussel M., Tubulin post-translational modifications: encoding functions on the neuronal microtubule cytoskeleton, Trends Neurosci., 2010, 33, 362–372

    Article  PubMed  CAS  Google Scholar 

  75. Fukushima N., Furuta D., Hidaka Y., Moriyama R., Tsujiuchi T., Posttranslational modifications of tubulin in the nervous system, J. Neurochem., 2009, 109, 683–693

    Article  PubMed  CAS  Google Scholar 

  76. Reed N. A., Cai D., Blasius T. L., Jih G. T., Meyhofer E., Gaertig J., et al., Microtubule acetylation promotes kinesin-1 binding and transport, Curr. Biol., 2006, 16, 2166–2172

    Article  PubMed  CAS  Google Scholar 

  77. Westermann S., Weber K., Post-translational modifications regulate microtubule function, Nat. Rev. Mol. Cell Biol., 2003, 4, 938–947

    Article  PubMed  CAS  Google Scholar 

  78. Konishi Y., Setou M., Tubulin tyrosination navigates the kinesin-1 motor domain to axons, Nat. Neurosci., 2009, 12, 559–567

    Article  PubMed  CAS  Google Scholar 

  79. Bettencourt da Cruz A., Schwarzel M., Schulze S., Niyyati M., Heisenberg M., Kretzschmar D., Disruption of the MAP1B-related protein FUTSCH leads to changes in the neuronal cytoskeleton, axonal transport defects, and progressive neurodegeneration in Drosophila, Mol. Biol. Cell, 2005, 16, 2433–2442

    Article  PubMed  CAS  Google Scholar 

  80. Fischer M., Kaech S., Knutti D., Matus A., Rapid actin-based plasticity in dendritic spines, Neuron, 1998, 20, 847–854

    Article  PubMed  CAS  Google Scholar 

  81. Matsuzaki M., Honkura N., Ellis-Davies G. C., Kasai H., Structural basis of long-term potentiation in single dendritic spines, Nature, 2004, 429, 761–766

    Article  PubMed  CAS  Google Scholar 

  82. Luo L., Hensch T. K., Ackerman L., Barbel S., Jan L. Y., Jan Y. N., Differential effects of the Rac GTPase on Purkinje cell axons and dendritic trunks and spines, Nature, 1996, 379, 837–840

    Article  PubMed  CAS  Google Scholar 

  83. McIlvain J. M. Jr., Burkhardt J. K., Hamm-Alvarez S., Argon Y., Sheetz M. P., Regulation of kinesin activity by phosphorylation of kinesinassociated proteins, J. Biol. Chem., 1994, 269, 19176–19182

    PubMed  CAS  Google Scholar 

  84. Lindesmith L., McIlvain J. M. Jr., Argon Y., Sheetz M. P., Phosphotransferases associated with the regulation of kinesin motor activity, J. Biol. Chem., 1997, 272, 22929–22933

    Article  PubMed  CAS  Google Scholar 

  85. Sheetz M. P., Motor and cargo interactions, Eur. J. Biochem., 1999, 262, 19–25

    Article  PubMed  CAS  Google Scholar 

  86. Morfini G., Pigino G., Szebenyi G., You Y., Pollema S., Brady S. T., JNK mediates pathogenic effects of polyglutamine-expanded androgen receptor on fast axonal transport, Nat. Neurosci., 2006, 9, 907–916

    Article  PubMed  CAS  Google Scholar 

  87. Stagi M., Gorlovoy P., Larionov S., Takahashi K., Neumann H., Unloading kinesin transported cargoes from the tubulin track via the inflammatory c-Jun N-terminal kinase pathway, FASEB J., 2006, 20, 2573–2575

    Article  PubMed  CAS  Google Scholar 

  88. Koushika S. P., “JIP”ing along the axon: the complex roles of JIPs in axonal transport, Bioessays, 2008, 30, 10–14

    Article  PubMed  CAS  Google Scholar 

  89. Blasius T. L., Cai D., Jih G. T., Toret C. P., Verhey K. J., Two binding partners cooperate to activate the molecular motor Kinesin-1, J. Cell Biol., 2007, 176, 11–17

    Article  PubMed  CAS  Google Scholar 

  90. Horiuchi D., Collins C. A., Bhat P., Barkus R. V., Diantonio A., Saxton W. M., Control of a kinesin-cargo linkage mechanism by JNK pathway kinases, Curr. Biol., 2007, 17, 1313–1317

    Article  PubMed  CAS  Google Scholar 

  91. Chang L., Jones Y., Ellisman M. H., Goldstein L. S., Karin M., JNK1 is required for maintenance of neuronal microtubules and controls phosphorylation of microtubule-associated proteins, Dev. Cell, 2003, 4, 521–533

    Article  PubMed  CAS  Google Scholar 

  92. Reynolds C. H., Utton M. A., Gibb G. M., Yates A., Anderton B. H., Stress-activated protein kinase/c-jun N-terminal kinase phosphorylates tau protein, J. Neurochem., 1997, 68, 1736–1744

    Article  PubMed  CAS  Google Scholar 

  93. Tararuk T., Ostman N., Li W., Bjorkblom B., Padzik A., Zdrojewska J., et al., JNK1 phosphorylation of SCG10 determines microtubule dynamics and axodendritic length, J. Cell Biol., 2006, 173, 265–277

    Article  PubMed  CAS  Google Scholar 

  94. Colin E., Zala D., Liot G., Rangone H., Borrell-Pages M., Li X. J., et al., Huntingtin phosphorylation acts as a molecular switch for anterograde/retrograde transport in neurons, EMBO J., 2008, 27, 2124–2134

    Article  PubMed  CAS  Google Scholar 

  95. Schaefer A. W., Schoonderwoert V. T., Ji L., Mederios N., Danuser G., Forscher P., Coordination of actin filament and microtubule dynamics during neurite outgrowth, Dev. Cell, 2008, 15, 146–162

    Article  PubMed  CAS  Google Scholar 

  96. Burnette D. T., Ji L., Schaefer A. W., Medeiros N. A., Danuser G., Forscher P., Myosin II activity facilitates microtubule bundling in the neuronal growth cone neck, Dev. Cell, 2008, pp15, 163–169

    Article  CAS  Google Scholar 

  97. Arimura N., Kaibuchi K., Neuronal polarity: from extracellular signals to intracellular mechanisms, Nat. Rev. Neurosci., 2007, 8, 194–205

    Article  PubMed  CAS  Google Scholar 

  98. Dent E. W., Gertler F. B., Cytoskeletal dynamics and transport in growth cone motility and axon guidance, Neuron, 2003, 40, 209–227

    Article  PubMed  CAS  Google Scholar 

  99. Mufson E. J., Kroin J. S., Sendera T. J., Sobreviela T., Distribution and retrograde transport of trophic factors in the central nervous system: functional implications for the treatment of neurodegenerative diseases, Prog. Neurobiol., 1999, 57, 451–484

    Article  PubMed  CAS  Google Scholar 

  100. Hirokawa N., Noda Y., Intracellular transport and kinesin superfamily proteins, KIFs: structure, function, and dynamics, Physiol. Rev., 2008, 88, 1089–1118

    Article  PubMed  CAS  Google Scholar 

  101. Kandel E. R., The molecular biology of memory storage: a dialogue between genes and synapses, Science, 2001, 294, 1030–1038

    Article  PubMed  CAS  Google Scholar 

  102. Kiebler M. A., DesGroseillers L., Molecular insights into mRNA transport and local translation in the mammalian nervous system, Neuron, 2000, 25, 19–28

    Article  PubMed  CAS  Google Scholar 

  103. Martin K. C., Casadio A., Zhu H., Yaping E., Rose J. C., Chen M., et al., Synapse-specific, long-term facilitation of aplysia sensory to motor synapses: a function for local protein synthesis in memory storage, Cell, 1997, 91, 927–938

    Article  PubMed  CAS  Google Scholar 

  104. Si K., Giustetto M., Etkin A., Hsu R., Janisiewicz A. M., Miniaci M. C., et al., A neuronal isoform of CPEB regulates local protein synthesis and stabilizes synapse-specific long-term facilitation in aplysia, Cell, 2003, 115, 893–904

    Article  PubMed  CAS  Google Scholar 

  105. Martin K. C., Ephrussi A., mRNA localization: gene expression in the spatial dimension, Cell, 2009, 136, 719–730

    Article  PubMed  CAS  Google Scholar 

  106. Tubing F., Vendra G., Mikl M., Macchi P., Thomas S., Kiebler M. A., Dendritically localized transcripts are sorted into distinct ribonucleoprotein particles that display fast directional motility along dendrites of hippocampal neurons, J. Neurosci., 2010, 30, 4160–4170

    Article  PubMed  CAS  Google Scholar 

  107. Lyles V., Zhao Y., Martin K. C., Synapse formation and mRNA localization in cultured Aplysia neurons, Neuron, 2006, 49, 349–356

    Article  PubMed  CAS  Google Scholar 

  108. Raymond C. R., Thompson V. L., Tate W. P., Abraham W. C., Metabotropic glutamate receptors trigger homosynaptic protein synthesis to prolong long-term potentiation, J. Neurosci., 2000, 20, 969–976

    PubMed  CAS  Google Scholar 

  109. Miki H., Okada Y., Hirokawa N., Analysis of the kinesin superfamily: insights into structure and function, Trends Cell Biol., 2005, 15, 467–476

    Article  PubMed  CAS  Google Scholar 

  110. Kanai Y., Dohmae N., Hirokawa N., Kinesin transports RNA: isolation and characterization of an RNA-transporting granule, Neuron, 2004, 43, 513–525

    Article  PubMed  CAS  Google Scholar 

  111. De Vos K. J., Grierson A. J., Ackerley S., Miller C. C., Role of axonal transport in neurodegenerative diseases, Annu. Rev. Neurosci., 2008, 31, 151–173

    Article  PubMed  CAS  Google Scholar 

  112. Pack-Chung E., Kurshan P. T., Dickman D. K., Schwarz T. L., A Drosophila kinesin required for synaptic bouton formation and synaptic vesicle transport, Nat. Neurosci., 2007, 10, 980–989

    Article  PubMed  CAS  Google Scholar 

  113. Horiuchi D., Barkus R. V., Pilling A. D., Gassman A., Saxton W. M., APLIP1, a kinesin binding JIP-1/JNK scaffold protein, influences the axonal transport of both vesicles and mitochondria in Drosophila, Curr. Biol., 2005, 15, 2137–2141

    Article  PubMed  CAS  Google Scholar 

  114. Miller K. E., DeProto J., Kaufmann N., Patel B. N., Duckworth A., Van Vactor D., Direct observation demonstrates that Liprin-alpha is required for trafficking of synaptic vesicles, Curr. Biol., 2005, 15, 684–689

    Article  PubMed  CAS  Google Scholar 

  115. Gindhart J. G., Chen J., Faulkner M., Gandhi R., Doerner K., Wisniewski T., et al., The kinesin-associated protein UNC-76 is required for axonal transport in the Drosophila nervous system, Mol. Biol. Cell, 2003, 14, 3356–3365

    Article  PubMed  CAS  Google Scholar 

  116. Glater E. E., Megeath L. J., Stowers R. S., Schwarz T. L., Axonal transport of mitochondria requires milton to recruit kinesin heavy chain and is light chain independent, J. Cell Biol., 2006, 173, 545–557

    Article  PubMed  CAS  Google Scholar 

  117. Hafezparast M., Klocke R., Ruhrberg C., Marquardt A., Ahmad-Annuar A., Bowen S., et al., Mutations in dynein link motor neuron degeneration to defects in retrograde transport, Science, 2003, 300, 808–812

    Article  PubMed  CAS  Google Scholar 

  118. Ori-McKenney K. M., Xu J., Gross S. P., Vallee R. B., A cytoplasmic dynein tail mutation impairs motor processivity, Nat. Cell Biol., 2010, 12, 1228–1234

    Article  PubMed  CAS  Google Scholar 

  119. Courchesne S. L., Pazyra-Murphy M. F., Lee D. J., Segal R. A., Neuromuscular junction defects in mice with mutation of dynein heavy chain 1, PLoS One, 2011, 6, e16753

    Article  PubMed  CAS  Google Scholar 

  120. Ilieva H. S. Yamanaka K., Malkmus S., Kakinohana O., Yaksh T., Marsala M., et al., Mutant dynein (Loa) triggers proprioceptive axon loss that extends survival only in the SOD1 ALS model with highest motor neuron death, Proc. Natl. Acad. Sci. USA, 2008, 105, 12599–12604

    Article  PubMed  CAS  Google Scholar 

  121. Braunstein K. E., Eschbach J., Rona-Voros K., Soylu R., Mikrouli E., Larmet Y., et al., A point mutation in the dynein heavy chain gene leads to striatal atrophy and compromises neurite outgrowth of striatal neurons, Hum. Mol. Genet., 2010, 19, 4385–4398

    Article  PubMed  CAS  Google Scholar 

  122. Jiang Y. M., Yamamoto M., Kobayashi Y., Yoshihara T., Liang Y., Terao S., et al., Gene expression profile of spinal motor neurons in sporadic amyotrophic lateral sclerosis, Ann. Neurol., 2005, 57, 236–251

    Article  PubMed  CAS  Google Scholar 

  123. Riviere J. B., Ramalingam S., Lavastre V., Shekarabi M., Holbert S., Lafontaine J., et al., KIF1A, an axonal transporter of synaptic vesicles, is mutated in hereditary sensory and autonomic neuropathy type 2, Am. J. Hum. Genet., 2011, 89, 219–230

    Article  PubMed  CAS  Google Scholar 

  124. Erlich Y., Edvardson S., Hodges E., Zenvirt S., Thekkat P., Shaag A., et al., Exome sequencing and disease-network analysis of a single family implicate a mutation in KIF1A in hereditary spastic paraparesis, Genome Res., 2011, 21, 658–664

    Article  PubMed  CAS  Google Scholar 

  125. Blair M. A., Ma S., Hedera P., Mutation in KIF5A can also cause adultonset hereditary spastic paraplegia, Neurogenetics, 2006, 7, 47–50

    Article  PubMed  CAS  Google Scholar 

  126. Dafinger C., Liebau M. C., Elsayed S. M., Hellenbroich Y., Boltshauser E., Korenke G. C., et al., Mutations in KIF7 link Joubert syndrome with Sonic Hedgehog signaling and microtubule dynamics, J. Clin. Invest., 2011, 121, 2662–2667

    Article  PubMed  CAS  Google Scholar 

  127. Tarabeux J., Champagne N., Brustein E., Hamdan F. F., Gauthier J., Lapointe M., et al., De novo truncating mutation in Kinesin 17 associated with schizophrenia, Biol. Psychiatry, 2010, 68, 649–656

    Article  PubMed  CAS  Google Scholar 

  128. Lu S., Zhao C., Zhao K., Li N., Larsson C., Novel and recurrent KIF21A mutations in congenital fibrosis of the extraocular muscles type 1 and 3, Arch. Ophthalmol., 2008, 126, 388–394

    Article  PubMed  CAS  Google Scholar 

  129. Khan A. O., Khalil D. S., Al Sharif L. J., Al-Ghadhfan F. E., Al Tassan N. A., Germline mosaicism for KIF21A mutation (p.R954L) mimicking recessive inheritance for congenital fibrosis of the extraocular muscles, Ophthalmology, 2010, 117, 154–158

    Article  PubMed  Google Scholar 

  130. Zhao C., Takita J., Tanaka Y., Setou M., Nakagawa T., Takeda S., et al., Charcot-Marie-Tooth disease type 2A caused by mutation in a microtubule motor KIF1Bbeta, Cell, 2001, 105, 587–597

    Article  PubMed  CAS  Google Scholar 

  131. Sharma R., Buras E., Terashima T., Serrano F., Massaad C. A., Hu L., et al., Hyperglycemia induces oxidative stress and impairs axonal transport rates in mice, PLoS One, 2010, 5, e13463

    Article  PubMed  CAS  Google Scholar 

  132. Haider L., Fischer M. T., Frischer J. M., Bauer J., Hoftberger R., Botond G., et al., Oxidative damage in multiple sclerosis lesions, Brain, 2011, 134, 1914–1924

    Article  PubMed  Google Scholar 

  133. Wilkinson A. E., Bridges L. R., Sivaloganathan S., Correlation of survival time with size of axonal swellings in diffuse axonal injury, Acta Neuropathol., 1999, 98, 197–202

    Article  PubMed  CAS  Google Scholar 

  134. Roediger B., Armati P. J., Oxidative stress induces axonal beading in cultured human brain tissue, Neurobiol. Dis., 2003, 13, 222–229

    Article  PubMed  CAS  Google Scholar 

  135. Stamer K., Vogel R., Thies E., Mandelkow E., Mandelkow E. M., Tau blocks traffic of organelles, neurofilaments, and APP vesicles in neurons and enhances oxidative stress, J. Cell Biol., 2002, 156, 1051–1063

    Article  PubMed  CAS  Google Scholar 

  136. Hirai K., Aliev G., Nunomura A., Fujioka H., Russell R. L., Atwood C. S., et al., Mitochondrial abnormalities in Alzheimer’s disease, J. Neurosci., 2001, 21, 3017–3023

    PubMed  CAS  Google Scholar 

  137. Massaad C. A., Amin S. K., Hu L., Mei Y., Klann E., Pautler R. G., Mitochondrial superoxide contributes to blood flow and axonal transport deficits in the Tg2576 mouse model of Alzheimer’s disease, PLoS One, 2010, 5, e10561

    Article  PubMed  CAS  Google Scholar 

  138. Shidara Y., Hollenbeck P. J., Defects in mitochondrial axonal transport and membrane potential without increased reactive oxygen species production in a Drosophila model of Friedreich ataxia, J. Neurosci., 2010, 30, 11369–11378

    Article  PubMed  CAS  Google Scholar 

  139. Green D. R., Reed J. C., Mitochondria and apoptosis, Science, 1998, 281, 1309–1312

    Article  PubMed  CAS  Google Scholar 

  140. Magrané J, Manfredi G., Mitochondrial function, morphology, and axonal transport in amyotrophic lateral sclerosis, Antioxid. Redox Signal., 2009, 11, 1615–1626

    Article  PubMed  Google Scholar 

  141. Sasaki S., Iwata M., Impairment of fast axonal transport in the proximal axons of anterior horn neurons in amyotrophic lateral sclerosis, Neurology, 1996, 47, 535–540

    Article  PubMed  CAS  Google Scholar 

  142. Sasaki S., Iwata M., Mitochondrial alterations in the spinal cord of patients with sporadic amyotrophic lateral sclerosis, J. Neuropathol. Exp. Neurol., 2007, 66, 10–16

    Article  PubMed  Google Scholar 

  143. Yue Z., Wang Q. J., Komatsu M., Neuronal autophagy: going the distance to the axon, Autophagy, 2008, 4, 94–96

    PubMed  Google Scholar 

  144. Katsumata K., Nishiyama J., Inoue T., Mizushima N., Takeda J., Yuzaki M., Dynein- and activity-dependent retrograde transport of autophagosomes in neuronal axons, Autophagy, 2010, 6, 378–385

    Article  PubMed  CAS  Google Scholar 

  145. Harris H., Rubinsztein D. C., Control of autophagy as a therapy for neurodegenerative disease, Nat. Rev. Neurol., 2012, 8, 108–117

    Article  CAS  Google Scholar 

  146. Nixon R. A., Autophagy in neurodegenerative disease: friend, foe or turncoat?, Trends Neurosci., 2006, 29, 528–535

    Article  PubMed  CAS  Google Scholar 

  147. Yu W. H., Cuervo A. M., Kumar A., Peterhoff C. M., Schmidt S. D., Lee J. H., et al., Macroautophagy — a novel beta-amyloid peptidegenerating pathway activated in Alzheimer’s disease, J. Cell Biol., 2005, 171, 87–98

    Article  PubMed  CAS  Google Scholar 

  148. Nixon R. A., Autophagy, amyloidogenesis and Alzheimer disease, J. Cell Sci., 2007, 120, 4081–4091

    Article  PubMed  CAS  Google Scholar 

  149. Chu C. T., Tickled PINK1: mitochondrial homeostasis and autophagy in recessive Parkinsonism, Biochim. Biophys. Acta, 2010, 1802, 20–28

    Article  PubMed  CAS  Google Scholar 

  150. Sapp E., Schwarz C., Chase K., Bhide P. G., Young A. B., Penney J., et al., Huntingtin localization in brains of normal and Huntington’s disease patients, Ann. Neurol., 1997, 42, 604–612

    Article  PubMed  CAS  Google Scholar 

  151. Martinez-Vicente M., Talloczy Z., Wong E., Tang G., Koga H., Kaushik S., et al., Cargo recognition failure is responsible for inefficient autophagy in Huntington’s disease, Nat. Neurosci., 2010, 13, 567–576

    Article  PubMed  CAS  Google Scholar 

  152. Sasaki S., Autophagy in spinal cord motor neurons in sporadic amyotrophic lateral sclerosis, J. Neuropathol. Exp. Neurol., 2011, 70, 349–359

    Article  PubMed  Google Scholar 

  153. Ravikumar B., Acevedo-Arozena A., Imarisio S., Berger Z., Vacher C., O’Kane C.J., et al., Dynein mutations impair autophagic clearance of aggregate-prone proteins, Nat. Genet., 2005, 37, 771–776

    Article  PubMed  CAS  Google Scholar 

  154. Laird F. M., Farah M. H., Ackerley S., Hoke A., Maragakis N., Rothstein J. D., et al., Motor neuron disease occurring in a mutant dynactin mouse model is characterized by defects in vesicular trafficking, J. Neurosci., 2008, 28, 1997–2005

    Article  PubMed  CAS  Google Scholar 

  155. Mattson M. P., Pathways towards and away from Alzheimer’s disease, Nature, 2004, 430, 631–639

    Article  PubMed  CAS  Google Scholar 

  156. Lee V.M., Goedert M., Trojanowski J. Q., Neurodegenerative tauopathies, Annu. Rev. Neurosci., 2001, 24, 1121–1159

    Article  PubMed  CAS  Google Scholar 

  157. Morris M., Maeda S., Vossel K., Mucke L., The many faces of tau, Neuron, 2011, 70, 410–426

    Article  PubMed  CAS  Google Scholar 

  158. Wang J. Z., Liu F., Microtubule-associated protein tau in development, degeneration and protection of neurons, Prog. Neurobiol., 2008, 85, 148–175

    Article  PubMed  CAS  Google Scholar 

  159. Hardy J., Selkoe D. J., The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics, Science, 2002, 297, 353–356

    Article  PubMed  CAS  Google Scholar 

  160. Vossel K. A., Zhang K., Brodbeck J., Daub A. C., Sharma P., Finkbeiner S., et al., Tau reduction prevents amyloid beta-induced defects in axonal transport, Science, 2010, 330, 198

    Article  PubMed  CAS  Google Scholar 

  161. Ittner L. M., Gotz J., Amyloid-beta and tau — a toxic pas de deux in Alzheimer’s disease, Nat. Rev. Neurosci., 2011, 12, 65–72

    Article  PubMed  CAS  Google Scholar 

  162. Reddy P. H., Abnormal tau, mitochondrial dysfunction, impaired axonal transport of mitochondria, and synaptic deprivation in Alzheimer’s disease, Brain. Res., 2011, 1415, 136–148

    Article  PubMed  CAS  Google Scholar 

  163. Spillantini M. G., Murrell J. R., Goedert M., Farlow M. R., Klug A., Ghetti B., Mutation in the tau gene in familial multiple system tauopathy with presenile dementia, Proc. Natl. Acad. Sci. USA, 1998, 95, 7737–7741

    Article  PubMed  CAS  Google Scholar 

  164. Cash A. D., Aliev G., Siedlak S. L., Nunomura A., Fujioka H., Zhu X., et al., Microtubule reduction in Alzheimer’s disease and aging is independent of tau filament formation, Am. J. Pathol., 2003, 162, 1623–1627

    Article  PubMed  CAS  Google Scholar 

  165. Khatoon S., Grundke-Iqbal I., Iqbal K., Brain levels of microtubuleassociated protein tau are elevated in Alzheimer’s disease: a radioimmuno-slot-blot assay for nanograms of the protein, J. Neurochem., 1992, 59, 750–753

    Article  PubMed  CAS  Google Scholar 

  166. Ebneth A., Godemann R., Stamer K., Illenberger S., Trinczek B., Mandelkow E., Overexpression of tau protein inhibits kinesindependent trafficking of vesicles, mitochondria, and endoplasmic reticulum: implications for Alzheimer’s disease, J. Cell Biol., 1998, 143, 777–794

    Article  PubMed  CAS  Google Scholar 

  167. Ishihara T., Hong M., Zhang B., Nakagawa Y., Lee M. K., Trojanowski J. Q., et al., Age-dependent emergence and progression of a tauopathy in transgenic mice overexpressing the shortest human tau isoform, Neuron, 1999, 24, 751–762

    Article  PubMed  CAS  Google Scholar 

  168. Ittner L. M., Fath T., Ke Y. D., Bi M., van Eersel J., Li K. M., et al., Parkinsonism and impaired axonal transport in a mouse model of frontotemporal dementia, Proc. Natl. Acad. Sci. USA, 2008, 105, 15997–16002

    Article  PubMed  CAS  Google Scholar 

  169. Probst A., Gotz J., Wiederhold K. H., Tolnay M., Mistl C., Jaton A. L., et al., Axonopathy and amyotrophy in mice transgenic for human four-repeat tau protein, Acta Neuropathol., 2000, 99, 469–481

    Article  PubMed  CAS  Google Scholar 

  170. Spittaels K., Van den Haute C., Van Dorpe J., Bruynseels K., Vandezande K., Laenen I., et al., Prominent axonopathy in the brain and spinal cord of transgenic mice overexpressing four-repeat human tau protein, Am. J. Pathol., 1999, 155, 2153–2165

    Article  PubMed  CAS  Google Scholar 

  171. Cote F., Collard J. F., Julien J. P., Progressive neuronopathy in transgenic mice expressing the human neurofilament heavy gene: a mouse model of amyotrophic lateral sclerosis, Cell, 1993, 73, 35–46

    Article  PubMed  CAS  Google Scholar 

  172. Xu Z., Cork L. C., Griffin J. W., Cleveland D. W., Increased expression of neurofilament subunit NF-L produces morphological alterations that resemble the pathology of human motor neuron disease, Cell, 1993, 73, 23–33

    Article  PubMed  CAS  Google Scholar 

  173. Zhang B., Higuchi M., Yoshiyama Y., Ishihara T., Forman M. S., Martinez D., et al., Retarded axonal transport of R406W mutant tau in transgenic mice with a neurodegenerative tauopathy, J. Neurosci., 2004, 24, 4657–4667

    Article  PubMed  CAS  Google Scholar 

  174. Higuchi M., Zhang B., Forman M. S., Yoshiyama Y., Trojanowski J. Q., Lee V. M., Axonal degeneration induced by targeted expression of mutant human tau in oligodendrocytes of transgenic mice that model glial tauopathies, J. Neurosci., 2005, 25, 9434–9443

    Article  PubMed  CAS  Google Scholar 

  175. Bull N. D., Guidi A., Goedert M., Martin K. R., Spillantini M. G., Reduced axonal transport and increased excitotoxic retinal ganglion cell degeneration in mice transgenic for human mutant P301S tau, PLoS One, 2012, 7, e34724

    Article  PubMed  CAS  Google Scholar 

  176. Dixit R., Ross J. L., Goldman Y. E., Holzbaur E. L., Differential regulation of dynein and kinesin motor proteins by tau, Science, 2008, 319, 1086–1089

    Article  PubMed  CAS  Google Scholar 

  177. Falzone T. L., Stokin G. B., Lillo C., Rodrigues E. M., Westerman E. L., Williams D. S., et al., Axonal stress kinase activation and tau misbehavior induced by kinesin-1 transport defects, J. Neurosci., 2009, 29, 5758–5767

    Article  PubMed  CAS  Google Scholar 

  178. Santacruz K., Lewis J., Spires T., Paulson J., Kotilinek L., Ingelsson M., et al., Tau suppression in a neurodegenerative mouse model improves memory function, Science, 2005, 309, 476–481

    Article  PubMed  CAS  Google Scholar 

  179. Lewis J., Dickson D. W., Lin W. L., Chisholm L., Corral A., Jones G., et al., Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP, Science, 2001, 293, 1487–1491

    Article  PubMed  CAS  Google Scholar 

  180. Roberson E. D., Scearce-Levie K., Palop J. J., Yan F., Cheng I. H., Wu T., et al., Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer’s disease mouse model, Science, 2007, 316, 750–754

    Article  PubMed  CAS  Google Scholar 

  181. Falzone T. L., Gunawardena S., McCleary D., Reis G. F., Goldstein L. S., Kinesin-1 transport reductions enhance human tau hyperphosphorylation, aggregation and neurodegeneration in animal models of tauopathies, Hum. Mol. Genet., 2010, 19, 4399–4408

    Article  PubMed  CAS  Google Scholar 

  182. Yuan A., Kumar A., Peterhoff C., Duff K., Nixon R. A., Axonal transport rates in vivo are unaffected by tau deletion or overexpression in mice, J. Neurosci., 2008, 28, 1682–1687

    Article  PubMed  CAS  Google Scholar 

  183. Kamal A., Stokin G. B., Yang Z, Xia C. H., Goldstein L. S., Axonal transport of amyloid precursor protein is mediated by direct binding to the kinesin light chain subunit of kinesin-I, Neuron, 2000, 28, 449–459

    Article  PubMed  CAS  Google Scholar 

  184. Stokin G. B., Lillo C., Falzone T. L., Brusch R. G., Rockenstein E., Mount S. L., et al., Axonopathy and transport deficits early in the pathogenesis of Alzheimer’s disease, Science, 2005, 307, 1282–1288

    Article  PubMed  CAS  Google Scholar 

  185. Wirths O., Weis J., Szczygielski J., Multhaup G., Bayer T. A., Axonopathy in an APP/PS1 transgenic mouse model of Alzheimer’s disease, Acta Neuropathol., 2006, 111, 312–319

    Article  PubMed  CAS  Google Scholar 

  186. Hiruma H., Katakura T., Takahashi S., Ichikawa T., Kawakami T., Glutamate and amyloid beta-protein rapidly inhibit fast axonal transport in cultured rat hippocampal neurons by different mechanisms, J. Neurosci., 2003, 23, 8967–8977

    PubMed  CAS  Google Scholar 

  187. Rui Y., Tiwari P., Xie Z., Zheng J. Q., Acute impairment of mitochondrial trafficking by beta-amyloid peptides in hippocampal neurons, J. Neurosci., 2006, 26, 10480–10487

    Article  PubMed  CAS  Google Scholar 

  188. Decker H., Lo K. Y., Unger S. M., Ferreira S. T., Silverman M. A., Amyloid-beta peptide oligomers disrupt axonal transport through an NMDA receptor-dependent mechanism that is mediated by glycogen synthase kinase 3beta in primary cultured hippocampal neurons, J. Neurosci., 2010, 30, 9166–9171

    PubMed  CAS  Google Scholar 

  189. Pigino G., Morfini G., Atagi Y., Deshpande A., Yu C., Jungbauer L., et al., Disruption of fast axonal transport is a pathogenic mechanism for intraneuronal amyloid beta, Proc. Natl. Acad. Sci. USA, 2009, 106, 5907–5912

    Article  PubMed  CAS  Google Scholar 

  190. Pigino G., Morfini G., Pelsman A., Mattson M. P., Brady S. T., Busciglio J., Alzheimer’s presenilin 1 mutations impair kinesin-based axonal transport, J. Neurosci., 2003, 23, 4499–4508

    PubMed  CAS  Google Scholar 

  191. Lazarov O., Morfini G. A., Pigino G., Gadadhar A., Chen X., Robinson J., et al., Impairments in fast axonal transport and motor neuron deficits in transgenic mice expressing familial Alzheimer’s diseaselinked mutant presenilin 1, J. Neurosci., 2007, 27, 7011–7020

    Article  PubMed  CAS  Google Scholar 

  192. Cai D., Leem J. Y., Greenfield J. P., Wang P., Kim B. S., Wang R., et al., Presenilin-1 regulates intracellular trafficking and cell surface delivery of beta-amyloid precursor protein, J. Biol. Chem., 2003, 278, 3446–3454

    Article  PubMed  CAS  Google Scholar 

  193. Tesseur I., Van Dorpe J., Bruynseels K., Bronfman F., Sciot R., Van Lommel A., et al., Prominent axonopathy and disruption of axonal transport in transgenic mice expressing human apolipoprotein E4 in neurons of brain and spinal cord, Am. J. Pathol., 2000, 157, 1495–1510

    Article  PubMed  CAS  Google Scholar 

  194. Haberland C., Frontotemporal dementia or frontotemporal lobar degeneration -overview of a group of proteinopathies, Ideggyogy Sz., 2010, 63, 87–93

    PubMed  Google Scholar 

  195. Fujioka S., Wszolek Z. K., Clinical aspects of familial forms of frontotemporal dementia associated with parkinsonism, J. Mol. Neurosci., 2011, 45, 359–365

    Article  PubMed  CAS  Google Scholar 

  196. Ghazi-Noori S., Froud K. E., Mizielinska S., Powell C., Smidak M., Fernandez de Marco M., et al., Progressive neuronal inclusion formation and axonal degeneration in CHMP2B mutant transgenic mice, Brain, 2012, 135, 819–832

    Article  PubMed  Google Scholar 

  197. Urwin H., Authier A., Nielsen J. E., Metcalf D., Powell C., Froud K., et al., Disruption of endocytic trafficking in frontotemporal dementia with CHMP2B mutations, Hum. Mol. Genet., 2010, 19, 2228–2238

    Article  PubMed  CAS  Google Scholar 

  198. Ittner L. M., Ke Y. D., Gotz J., Phosphorylated Tau interacts with c-Jun N-terminal kinase-interacting protein 1 (JIP1) in Alzheimer disease, J. Biol. Chem., 2009, 284, 20909–20916

    Article  PubMed  CAS  Google Scholar 

  199. Magnani E., Fan J., Gasparini L., Golding M., Williams M., Schiavo G., et al., Interaction of tau protein with the dynactin complex, EMBO J., 2007, 26, 4546–4554

    Article  PubMed  CAS  Google Scholar 

  200. Hong M., Zhukareva V., Vogelsberg-Ragaglia V., Wszolek Z., Reed L., Miller B. I., et al., Mutation-specific functional impairments in distinct tau isoforms of hereditary FTDP-17, Science, 1998, 282, 1914–1917

    Article  PubMed  CAS  Google Scholar 

  201. Stoothoff W., Jones P. B., Spires-Jones T. L., Joyner D., Chhabra E., Bercury K., et al., Differential effect of three-repeat and four-repeat tau on mitochondrial axonal transport, J. Neurochem., 2009, 111, 417–427

    Article  PubMed  CAS  Google Scholar 

  202. Tien N. W., Wu G. H., Hsu C. C., Chang C. Y., Wagner O. I., Tau/PTL-1 associates with kinesin-3 KIF1A/UNC-104 and affects the motor’s motility characteristics in C. elegans neurons, Neurobiol. Dis., 2011, 43, 495–506

    Article  PubMed  CAS  Google Scholar 

  203. Gilley J., Seereeram A., Ando K., Mosely S., Andrews S., Kerschensteiner M., et al., Age-dependent axonal transport and locomotor changes and tau hypophosphorylation in a “P301L” tau knockin mouse, Neurobiol. Aging, 2012, 33, 621.e1–621.e15

    Article  CAS  Google Scholar 

  204. Mulder D. W., Clinical limits of amyotrophic lateral sclerosis, Adv. Neurol., 1982, 36, 15–22

    PubMed  CAS  Google Scholar 

  205. Rowland L. P., Shneider N. A., Amyotrophic lateral sclerosis, N. Engl. J. Med., 2001, 344, 1688–1700

    Article  PubMed  CAS  Google Scholar 

  206. Rosen D. R., Siddique T., Patterson D., Figlewicz D. A., Sapp P., Hentati A., et al., Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis, Nature, 1993, 362, 59–62

    Article  PubMed  CAS  Google Scholar 

  207. Zhang B., Tu P., Abtahian F., Trojanowski J. Q., Lee V. M., Neurofilaments and orthograde transport are reduced in ventral root axons of transgenic mice that express human SOD1 with a G93A mutation, J. Cell Biol., 1997, 139, 1307–1315

    Article  PubMed  CAS  Google Scholar 

  208. Williamson T. L., Cleveland D. W., Slowing of axonal transport is a very early event in the toxicity of ALS-linked SOD1 mutants to motor neurons, Nat. Neurosci., 1999, 2, 50–56

    Article  PubMed  CAS  Google Scholar 

  209. Borchelt D. R., Wong P. C., Becher M. W., Pardo C. A., Lee M. K., Xu Z. S., et al., Axonal transport of mutant superoxide dismutase 1 and focal axonal abnormalities in the proximal axons of transgenic mice, Neurobiol. Dis., 1998, 5, 27–35

    Article  PubMed  CAS  Google Scholar 

  210. Tateno M., Kato S., Sakurai T., Nukina N., Takahashi R., Araki T., Mutant SOD1 impairs axonal transport of choline acetyltransferase and acetylcholine release by sequestering KAP3, Hum. Mol. Genet., 2009, 18, 942–955

    PubMed  CAS  Google Scholar 

  211. Landers J. E., Melki J., Meininger V., Glass J. D., van den Berg L. H., van Es M. A., et al., Reduced expression of the Kinesin-Associated Protein 3 (KIFAP3) gene increases survival in sporadic amyotrophic lateral sclerosis, Proc. Natl. Acad. Sci. USA, 2009, 106, 9004–9009

    Article  PubMed  CAS  Google Scholar 

  212. Dupuis L., de Tapia M., Rene F., Lutz-Bucher B., Gordon J. W., Mercken L., et al., Differential screening of mutated SOD1 transgenic mice reveals early up-regulation of a fast axonal transport component in spinal cord motor neurons, Neurobiol. Dis., 2000, 7, 274–285

    Article  PubMed  CAS  Google Scholar 

  213. Murakami T., Nagano I., Hayashi T., Manabe Y., Shoji M., Setoguchi Y., et al., Impaired retrograde axonal transport of adenovirusmediated E. coli LacZ gene in the mice carrying mutant SOD1 gene, Neurosci. Lett., 2001, 308, 149–152

    Article  PubMed  CAS  Google Scholar 

  214. Ligon L. A., LaMonte B. H., Wallace K. E., Weber N., Kalb R. G., Holzbaur E. L., Mutant superoxide dismutase disrupts cytoplasmic dynein in motor neurons, Neuroreport, 2005, 16, 533–536

    Article  PubMed  CAS  Google Scholar 

  215. Bilsland L. G., Sahai E., Kelly G., Golding M., Greensmith L., Schiavo G., Deficits in axonal transport precede ALS symptoms in vivo, Proc. Natl. Acad. Sci. USA, 2010, 107, 20523–20528

    Article  PubMed  CAS  Google Scholar 

  216. Munch C., Sedlmeier R., Meyer T., Homberg V., Sperfeld A. D., Kurt A., et al., Point mutations of the p150 subunit of dynactin (DCTN1) gene in ALS, Neurology, 2004, 63, 724–726

    Article  PubMed  CAS  Google Scholar 

  217. Moore J. K., Sept D., Cooper J. A., Neurodegeneration mutations in dynactin impair dynein-dependent nuclear migration, Proc. Natl. Acad. Sci. USA, 2009, 106, 5147–5152

    Article  PubMed  CAS  Google Scholar 

  218. Pasinelli P., Brown R. H., Molecular biology of amyotrophic lateral sclerosis: insights from genetics, Nat. Rev. Neurosci., 2006, 7, 710–723

    Article  PubMed  CAS  Google Scholar 

  219. Puls I., Jonnakuty C., LaMonte B. H., Holzbaur E. L., Tokito M., Mann E., et al., Mutant dynactin in motor neuron disease, Nat. Genet., 2003, 33, 455–456

    Article  PubMed  CAS  Google Scholar 

  220. Teuchert M., Fischer D., Schwalenstoecker B., Habisch H. J., Bockers T. M., Ludolph A. C., A dynein mutation attenuates motor neuron degeneration in SOD1(G93A) mice, Exp. Neurol., 2006, 198, 271–274

    Article  PubMed  CAS  Google Scholar 

  221. Kieran D., Hafezparast M., Bohnert S., Dick J. R., Martin J., Schiavo G., et al., A mutation in dynein rescues axonal transport defects and extends the life span of ALS mice, J. Cell Biol., 2005, 169, 561–567

    Article  PubMed  CAS  Google Scholar 

  222. Teuling E., van Dis V., Wulf P. S., Haasdijk E. D., Akhmanova A., Hoogenraad C. C., et al., 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., 2008, 17, 2849–2862

    Article  PubMed  CAS  Google Scholar 

  223. LaMonte B. H., Wallace K. E., Holloway B. A., Shelly S. S., Ascano J., Tokito M., et al., Disruption of dynein/dynactin inhibits axonal transport in motor neurons causing late-onset progressive degeneration, Neuron, 2002, 34, 715–727

    Article  PubMed  CAS  Google Scholar 

  224. Gepner J., Li M., Ludmann S., Kortas C., Boylan K., Iyadurai S. J., et al., Cytoplasmic dynein function is essential in Drosophila melanogaster, Genetics, 1996, 142, 865–878

    PubMed  CAS  Google Scholar 

  225. Chevalier-Larsen E. S., Wallace K. E., Pennise C. R., Holzbaur E. L., Lysosomal proliferation and distal degeneration in motor neurons expressing the G59S mutation in the p150Glued subunit of dynactin, Hum. Mol. Genet., 2008, 17, 1946–1955

    Article  PubMed  CAS  Google Scholar 

  226. Robertson J., Doroudchi M. M., Nguyen M. D., Durham H. D., Strong M. J., Shaw G., et al., A neurotoxic peripherin splice variant in a mouse model of ALS, J. Cell Biol., 2003, 160, 939–949

    Article  PubMed  CAS  Google Scholar 

  227. Kong J., Xu Z., Massive mitochondrial degeneration in motor neurons triggers the onset of amyotrophic lateral sclerosis in mice expressing a mutant SOD1, J. Neurosci., 1998, 18, 3241–3250

    PubMed  CAS  Google Scholar 

  228. Marinkovic P., Reuter M. S., Brill M. S., Godinho L., Kerschensteiner M., Misgeld T., Axonal transport deficits and degeneration can evolve independently in mouse models of amyotrophic lateral sclerosis, Proc. Natl. Acad. Sci. USA, 2012, 109, 4296–4301

    PubMed  CAS  Google Scholar 

  229. Bendotti C., Atzori C., Piva R., Tortarolo M., Strong M. J., DeBiasi S., Migheli A., Activated p38MAPK is a novel component of the intracellular inclusions found in human amyotrophic lateral sclerosis and mutant SOD1 transgenic mice, J. Neuropathol. Exp. Neurol., 2004, 63, 113–119

    PubMed  CAS  Google Scholar 

  230. Tortarolo M., Veglianese P., Calvaresi N., Botturi A., Rossi C., Giorgini A., et al., Persistent activation of p38 mitogen-activated protein kinase in a mouse model of familial amyotrophic lateral sclerosis correlates with disease progression, Mol. Cell. Neurosci., 2003, 23, 180–192

    Article  PubMed  CAS  Google Scholar 

  231. Morfini G. A., Burns M., Binder L. I., Kanaan N. M., LaPointe N., Bosco D. A., et al., Axonal transport defects in neurodegenerative diseases, J. Neurosci., 2009, 29, 12776–12786

    Article  PubMed  CAS  Google Scholar 

  232. Pizzuti A., Petrucci S., Mitochondrial disfunction as a cause of ALS, Arch. Ital. Biol., 2011, 149, 113–119

    PubMed  Google Scholar 

  233. Rothstein J. D., Excitotoxicity hypothesis, Neurology, 1996, 47, S19–25; discussion S26

    Article  PubMed  CAS  Google Scholar 

  234. Wiedau-Pazos M., Goto J. J., Rabizadeh S., Gralla E. B., Roe J. A., Lee M. K., et al., Altered reactivity of superoxide dismutase in familial amyotrophic lateral sclerosis, Science, 1996, 271, 515–518

    Article  PubMed  CAS  Google Scholar 

  235. Zhang Y., Marcillat O., Giulivi C., Ernster L., Davies K. J., The oxidative inactivation of mitochondrial electron transport chain components and ATPase, J. Biol. Chem., 1990, 265, 16330–16336

    PubMed  CAS  Google Scholar 

  236. Salinas S., Proukakis C., Crosby A., Warner T. T., Hereditary spastic paraplegia: clinical features and pathogenetic mechanisms, Lancet Neurol., 2008, 7, 1127–1138

    Article  PubMed  CAS  Google Scholar 

  237. Blackstone C., O’Kane C. J., Reid E., Hereditary spastic paraplegias: membrane traffic and the motor pathway, Nat. Rev. Neurosci., 2011, 12, 31–42

    Article  PubMed  CAS  Google Scholar 

  238. Reid E., Kloos M., Ashley-Koch A., Hughes L., Bevan S., Svenson I. K., et al., A kinesin heavy chain (KIF5A) mutation in hereditary spastic paraplegia (SPG10), Am. J. Hum. Genet., 2002, 71, 1189–1194

    Article  PubMed  CAS  Google Scholar 

  239. Fichera M., Lo Giudice M., Falco M., Sturnio M., Amata S., Calabrese O., et al., Evidence of kinesin heavy chain (KIF5A) involvement in pure hereditary spastic paraplegia, Neurology, 2004, 63, 1108–1110

    Article  PubMed  CAS  Google Scholar 

  240. Ebbing B., Mann K., Starosta A., Jaud J., Schols L., Schule R., et al., Effect of spastic paraplegia mutations in KIF5A kinesin on transport activity, Hum. Mol. Genet., 2008, 17, 1245–1252

    Article  PubMed  CAS  Google Scholar 

  241. Ferreirinha F., Quattrini A., Pirozzi M., Valsecchi V., Dina G., Broccoli V., et al., Axonal degeneration in paraplegin-deficient mice is associated with abnormal mitochondria and impairment of axonal transport, J. Clin. Invest., 2004, 113, 231–242

    PubMed  CAS  Google Scholar 

  242. Baas P. W., Karabay A., Qiang L., Microtubules cut and run, Trends Cell Biol., 2005, 15, 518–524

    Article  PubMed  CAS  Google Scholar 

  243. Zhao X., Alvarado D., Rainier S., Lemons R., Hedera P., Weber C. H., et al., Mutations in a newly identified GTPase gene cause autosomal dominant hereditary spastic paraplegia, Nat. Genet., 2001, 29, 326–331

    Article  PubMed  CAS  Google Scholar 

  244. Hazan J., Fonknechten N., Mavel D., Paternotte C., Samson D., Artiguenave F., et al., Spastin, a new AAA protein, is altered in the most frequent form of autosomal dominant spastic paraplegia, Nat. Genet., 1999, 23, 296–303

    Article  PubMed  CAS  Google Scholar 

  245. Goizet C., Depienne C., Benard G., Boukhris A., Mundwiller E., Sole G., et al., REEP1 mutations in SPG31: frequency, mutational spectrum, and potential association with mitochondrial morphofunctional dysfunction, Hum. Mutat., 2011, 32, 1118–1127

    Article  PubMed  CAS  Google Scholar 

  246. Kasher P. R., De Vos K. J., Wharton S. B., Manser C., Bennett E. J., Bingley M., et al., Direct evidence for axonal transport defects in a novel mouse model of mutant spastin-induced hereditary spastic paraplegia (HSP) and human HSP patients, J. Neurochem., 2009, 110, 34–44

    Article  PubMed  CAS  Google Scholar 

  247. Tarrade A., Fassier C., Courageot S., Charvin D., Vitte J., Peris L., et al., A mutation of spastin is responsible for swellings and impairment of transport in a region of axon characterized by changes in microtubule composition, Hum. Mol. Genet., 2006, 15, 3544–3558

    Article  PubMed  CAS  Google Scholar 

  248. Zuchner S., Vance J. M., Mechanisms of disease: a molecular genetic update on hereditary axonal neuropathies, Nat. Clin. Pract. Neurol., 2006, 2, 45–53

    Article  PubMed  CAS  Google Scholar 

  249. Crimella C., Baschirotto C., Arnoldi A., Tonelli A., Tenderini E., Airoldi G., et al., Mutations in the motor and stalk domains of KIF5A in spastic paraplegia type 10 and in axonal Charcot-Marie-Tooth type 2, Clin. Genet., 2011

  250. Willemsen M. H., Vissers L. E., Willemsen M. A., van Bon B. W., Kroes T., de Ligt J., et al., Mutations in DYNC1H1 cause severe intellectual disability with neuronal migration defects, J. Med. Genet., 2012, 49, 179–183

    Article  PubMed  CAS  Google Scholar 

  251. d’Ydewalle C., Krishnan J., Chiheb D.M., Van Damme P., Irobi J., Kozikowski A.P., et al., HDAC6 inhibitors reverse axonal loss in a mouse model of mutant HSPB1-induced Charcot-Marie-Tooth disease, Nat. Med., 2011, 17, 968–974

    Article  PubMed  CAS  Google Scholar 

  252. Estela A., Pla-Martin D., Sanchez-Piris M., Sesaki H., Palau F., Charcot-Marie-Tooth-related gene GDAP1 complements cell cycle delay at G2/M phase in Saccharomyces cerevisiae fis1 gene-defective cells, J. Biol. Chem., 2011, 286, 36777–36786

    Article  PubMed  CAS  Google Scholar 

  253. Cassereau J., Chevrollier A., Gueguen N., Desquiret V., Verny C., Nicolas G., et al., Mitochondrial dysfunction and pathophysiology of Charcot-Marie-Tooth disease involving GDAP1 mutations, Exp. Neurol., 2011, 227, 31–41

    Article  PubMed  CAS  Google Scholar 

  254. Warren G., Wickner W., Organelle inheritance, Cell, 1996, 84, 395–400

    Article  PubMed  CAS  Google Scholar 

  255. Kabzinska D., Niemann A., Drac H., Huber N., Potulska-Chromik A., Hausmanowa-Petrusewicz I., et al., A new missense GDAP1 mutation disturbing targeting to the mitochondrial membrane causes a severe form of AR-CMT2C disease, Neurogenetics, 2011, 12, 145–153

    Article  PubMed  CAS  Google Scholar 

  256. Baxter R. V., Ben Othmane K., Rochelle J. M., Stajich J. E., Hulette C., Dew-Knight S., et al., Ganglioside-induced differentiationassociated protein-1 is mutant in Charcot-Marie-Tooth disease type 4A/8q21, Nat. Genet., 2002, 30, 21–22

    Article  PubMed  CAS  Google Scholar 

  257. Misko A., Jiang, S., Wegorzewska, I., Milbrandt, J., Baloh, R. H., Mitofusin 2 is necessary for transport of axonal mitochondria and interacts with the Miro/Milton complex, J. Neurosci., 2010, 30, 4232–4240

    Article  PubMed  CAS  Google Scholar 

  258. Davies S. W., Turmaine M., Cozens B. A., DiFiglia M., Sharp A. H., Ross C. A., et al., Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation, Cell, 1997, 90, 537–548

    Article  PubMed  CAS  Google Scholar 

  259. Shirendeb U. P., Calkins M. J., Manczak M., Anekonda V., Dufour B., McBride J. L., et al., Mutant huntingtin’s interaction with mitochondrial protein Drp1 impairs mitochondrial biogenesis and causes defective axonal transport and synaptic degeneration in Huntington’s disease, Hum. Mol. Genet., 2012, 21, 406–420

    Article  PubMed  CAS  Google Scholar 

  260. Morfini G. A., You Y. M., Pollema S. L., Kaminska A., Liu K., Yoshioka K., et al., Pathogenic huntingtin inhibits fast axonal transport by activating JNK3 and phosphorylating kinesin, Nat. Neurosci., 2009, 12, 864–871

    Article  PubMed  CAS  Google Scholar 

  261. Gunawardena S., Her L. S., Brusch R. G., Laymon R. A., Niesman I. R., Gordesky-Gold B., et al., Disruption of axonal transport by loss of huntingtin or expression of pathogenic polyQ proteins in Drosophila, Neuron, 2003, 40, 25–40

    Article  PubMed  CAS  Google Scholar 

  262. Hurd D. D., Saxton W. M., Kinesin mutations cause motor neuron disease phenotypes by disrupting fast axonal transport in Drosophila, Genetics, 1996, 144, 1075–1085

    PubMed  CAS  Google Scholar 

  263. Ticozzi N., Ratti A., Silani V., Protein aggregation and defective RNA metabolism as mechanisms for motor neuron damage, CNS Neurol. Disord. Drug Targets, 2010, 9, 285–296

    Article  PubMed  CAS  Google Scholar 

  264. Weedon M. N., Hastings R., Caswell R., Xie W., Paszkiewicz K., Antoniadi T., et al., Exome sequencing identifies a DYNC1H1 mutation in a large pedigree with dominant axonal Charcot-Marie-Tooth disease, Am. J. Hum. Genet., 2011, 89, 308–312

    Article  PubMed  CAS  Google Scholar 

  265. Piccioni F., Pinton P., Simeoni S., Pozzi P., Fascio U., Vismara G., et al., Androgen receptor with elongated polyglutamine tract forms aggregates that alter axonal trafficking and mitochondrial distribution in motor neuronal processes, FASEB J., 2002, 16, 1418–1420

    PubMed  CAS  Google Scholar 

  266. Kemp M. Q., Poort J. L., Baqri R. M., Lieberman A. P., Breedlove S. M., Miller K. E., et al., Impaired motoneuronal retrograde transport in two models of SBMA implicates two sites of androgen action, Hum. Mol. Genet., 2011, 20, 4475–4490

    Article  PubMed  CAS  Google Scholar 

  267. La Spada A. R., Wilson E. M., Lubahn D. B., Harding A. E., Fischbeck K. H., Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy, Nature, 1991, 352, 77–79

    Article  PubMed  Google Scholar 

  268. Saha A. R., Hill J., Utton M. A., Asuni A. A., Ackerley S., Grierson A. J., et al., Parkinson’s disease alpha-synuclein mutations exhibit defective axonal transport in cultured neurons, J. Cell Sci., 2004, 117, 1017–1024

    Article  PubMed  CAS  Google Scholar 

  269. Abou-Sleiman P. M., Muqit M. M., Wood N. W., Expanding insights of mitochondrial dysfunction in Parkinson’s disease, Nat. Rev. Neurosci., 2006, 7, 207–219

    Article  PubMed  CAS  Google Scholar 

  270. Miller K. E., Sheetz M. P., Axonal mitochondrial transport and potential are correlated, J. Cell Sci., 2004, 117, 2791–2804

    Article  PubMed  CAS  Google Scholar 

  271. Morfini G., Pigino G., Opalach K., Serulle Y., Moreira J. E., Sugimori M., et al., 1-Methyl-4-phenylpyridinium affects fast axonal transport by activation of caspase and protein kinase C, Proc. Natl. Acad. Sci. USA, 2007, 104, 2442–2447

    Article  PubMed  CAS  Google Scholar 

  272. Su K. G., Banker G., Bourdette D., Forte M., Axonal degeneration in multiple sclerosis: the mitochondrial hypothesis, Curr. Neurol. Neurosci. Rep., 2009, 9, 411–417

    Article  PubMed  CAS  Google Scholar 

  273. Pagliardini S., Giavazzi A., Setola V., Lizier C., Di Luca M., DeBiasi S., et al., Subcellular localization and axonal transport of the survival motor neuron (SMN) protein in the developing rat spinal cord, Hum. Mol. Genet., 2000, 9, 47–56

    Article  PubMed  CAS  Google Scholar 

  274. Fallini C., Bassell G. J., Rossoll W., Spinal muscular atrophy: The role of SMN in axonal mRNA regulation, Brain Res., 2012, 1462, 81–92

    Article  PubMed  CAS  Google Scholar 

  275. Morfini G., Pigino G., Brady S. T., Polyglutamine expansion diseases: failing to deliver, Trends Mol. Med., 2005, 11, 64–70

    Article  PubMed  CAS  Google Scholar 

  276. Takahashi T., Katada S., Onodera O., Polyglutamine diseases: where does toxicity come from? What is toxicity? Where are we going?, J. Mol. Cell. Biol., 2010, 2, 180–191

    Article  PubMed  CAS  Google Scholar 

  277. Feany M. B., La Spada A. R., Polyglutamines stop traffic: axonal transport as a common target in neurodegenerative diseases, Neuron, 2003, 40, 1–2

    Article  PubMed  CAS  Google Scholar 

  278. Ermolayev V., Cathomen T., Merk J., Friedrich M., Hartig W., Harms G. S., et al., Impaired axonal transport in motor neurons correlates with clinical prion disease, PLoS Pathog., 2009, 5, e1000558

    Article  PubMed  CAS  Google Scholar 

  279. Almasieh M., Wilson A. M., Morquette B., Cueva Vargas J. L., Di Polo A., The molecular basis of retinal ganglion cell death in glaucoma, Prog. Retin. Eye Res., 2012, 31, 152–181

    Article  PubMed  CAS  Google Scholar 

  280. Lorenzo D. N., Li M. G., Mische S. E., Armbrust K. R., Ranum L. P., Hays T. S., Spectrin mutations that cause spinocerebellar ataxia type 5 impair axonal transport and induce neurodegeneration in Drosophila, J. Cell Biol., 2010, 189, 143–158

    Article  PubMed  CAS  Google Scholar 

  281. Smith D. H., Uryu K., Saatman K. E., Trojanowski J. Q., McIntosh T. K., Protein accumulation in traumatic brain injury, Neuromolecular Med., 2003, 4, 59–72

    Article  PubMed  CAS  Google Scholar 

  282. Bernier G., Kothary R., Prenatal onset of axonopathy in Dystonia musculorum mice, Dev. Genet., 1998, 22, 160–168

    Article  PubMed  CAS  Google Scholar 

  283. Furlong R. A., Zhou C. Y., Ferguson-Smith M. A., Affara N. A., Characterization of a kinesin-related gene ATSV, within the tuberous sclerosis locus (TSC1) candidate region on chromosome 9Q34, Genomics, 1996, 33, 421–429

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Neuroscience, The Scripps Research Institute, Scripps Florida, 130 Scripps Way, Jupiter, Fl-33458, USA

    Xin-An Liu, Valerio Rizzo & Sathyanarayanan V. Puthanveettil

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Liu, XA., Rizzo, V. & Puthanveettil, S.V. Pathologies of axonal transport in neurodegenerative diseases. Translat.Neurosci. 3, 355–372 (2012). https://doi.org/10.2478/s13380-012-0044-7

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