Abstract
The neuronal cytoskeleton not only provides the structural backbone of neurons, but also plays a fundamental role in maintaining neuronal functions. Dysregulation of neuronal architecture is evident in both injury and diseases of the central nervous system. These changes often result in the disruption of protein trafficking, loss of synapses and the death of neurons, ultimately impacting on signal transmission and manifesting in the disease phenotype. Furthermore, mutations in cytoskeletal proteins have been implicated in numerous diseases and, in some cases, identified as the cause of the disease, highlighting the critical role of the cytoskeleton in disease pathology. This review focuses on the role of cytoskeletal proteins in the pathology of mental disorders, neurodegenerative diseases and motor function deficits. In particular, we illustrate how cytoskeletal proteins can be directly linked to disease pathology and progression.
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Al-Chalabi A, Andersen P M, Nilsson P, Chioza B, Andersson J L, Russ C, Shaw C E, Powell J F, Leigh P N (1999). Deletions of the heavy neurofilament subunit tail in amyotrophic lateral sclerosis. Hum Mol Genet, 8(2): 157–164
Anderson S A, Volk D W, Lewis D A (1996). Increased density of microtubule associated protein 2-immunoreactive neurons in the prefrontal white matter of schizophrenic subjects. Schizophr Res, 19(2–3): 111–119
Andrianantoandro E, Pollard T D (2006). Mechanism of actin filament turnover by severing and nucleation at different concentrations of ADF/cofilin. Mol Cell, 24(1): 13–23
Andrieux A, Salin P A, Vernet M, Kujala P, Baratier J, Gory-Fauré S, Bosc C, Pointu H, Proietto D, Schweitzer A, Denarier E, Klumperman J, Job D (2002). The suppression of brain cold-stable microtubules in mice induces synaptic defects associated with neuroleptic-sensitive behavioral disorders. Genes Dev, 16(18): 2350–2364
Arber S, Barbayannis F A, Hanser H, Schneider C, Stanyon C A, Bernard O, Caroni P (1998). Regulation of actin dynamics through phosphorylation of cofilin by LIM-kinase. Nature, 393(6687): 805–809
Armstrong R A, Cairns N J (2012). Different molecular pathologies result in similar spatial patterns of cellular inclusions in neurode-generative disease: a comparative study of eight disorders. J Neural Transm, 119(12): 1551–1560
Armstrong R A, Kerty E, Skullerud K, Cairns N J (2006). Neuropathological changes in ten cases of neuronal intermediate filament inclusion disease (NIFID): a study using alpha-internexin immunohistochemistry and principal components analysis (PCA). J Neural Transm, 113(9): 1207–1215
Asbury A K, Gale M K, Cox S C, Baringer J R, Berg B O (1972). Giant axonal neuropathy—a unique case with segmental neurofilamentous masses. Acta Neuropathol, 20(3): 237–247
Asrar S, Meng Y, Zhou Z, Todorovski Z, Huang W W, Jia Z (2009). Regulation of hippocampal long-term potentiation by p21-activated protein kinase 1 (PAK1). Neuropharmacology, 56(1): 73–80
Baas P W, Ahmad F J (2013). Beyond taxol: microtubule-based treatment of disease and injury of the nervous system. Brain, 136(Pt 10): 2937–2951
Ballatore C, Lee V M, Trojanowski J Q (2007). Tau-mediated neurodegeneration in Alzheimer’s disease and related disorders. Nat Rev Neurosci, 8(9): 663–672
Bégou M, Brun P, Bertrand J B, Job D, Schweitzer A, D’Amato T, Saoud M, Andrieux A, Suaud-Chagny M F (2007). Post-pubertal emergence of alterations in locomotor activity in stop null mice. Synapse, 61(9): 689–697
Bégou M, Volle J, Bertrand J B, Brun P, Job D, Schweitzer A, Saoud M, D’Amato T, Andrieux A, Suaud-Chagny M F (2008). The stop null mice model for schizophrenia displays [corrected] cognitive and social deficits partly alleviated by neuroleptics. Neuroscience, 157(1): 29–39
Belichenko P V, Dahlström A (1995). Studies on the 3-dimensional architecture of dendritic spines and varicosities in human cortex by confocal laser scanning microscopy and Lucifer yellow microinjections. J Neurosci Methods, 57(1): 55–61
Bento-Abreu A, Van Damme P, Van Den Bosch L, Robberecht W (2010). The neurobiology of amyotrophic lateral sclerosis. Eur J Neurosci, 31(12): 2247–2265
Bergeron C, Beric-Maskarel K, Muntasser S, Weyer L, Somerville M J, Percy M E (1994). Neurofilament light and polyadenylated mRNA levels are decreased in amyotrophic lateral sclerosis motor neurons. J Neuropathol Exp Neurol, 53(3): 221–230
Bernhardt R, Matus A (1984). Light and electron microscopic studies of the distribution of microtubule-associated protein 2 in rat brain: a difference between dendritic and axonal cytoskeletons. J Comp Neurol, 226(2): 203–221
Bishop A L, Hall A (2000). Rho GTPases and their effector proteins. Biochem J, 348(Pt 2): 241–255
Bloom G S, Vallee R B (1983). Association of microtubule-associated protein 2 (MAP 2) with microtubules and intermediate filaments in cultured brain cells. J Cell Biol, 96(6): 1523–1531
Bocquet A, Berges R, Frank R, Robert P, Peterson A C, Eyer J (2009). Neurofilaments bind tubulin and modulate its polymerization. J Neurosci, 29(35): 11043–11054
Bosch M, Hayashi Y (2012). Structural plasticity of dendritic spines. Curr Opin Neurobiol, 22(3): 383–388
Brettschneider J, Petzold A, Süssmuth S D, Ludolph A C, Tumani H (2006). Axonal damage markers in cerebrospinal fluid are increased in ALS. Neurology, 66(6): 852–856
Brun P, Bégou M, Andrieux A, Mouly-Badina L, Clerget M, Schweitzer A, Scarna H, Renaud B, Job D, Suaud-Chagny M F (2005). Dopaminergic transmission in STOP null mice. J Neurochem, 94(1): 63–73
Brunden K R, Zhang B, Carroll J, Yao Y, Potuzak J S, Hogan A M, Iba M, James M J, Xie S X, Ballatore C, Smith A B 3rd, Lee V M Y, Trojanowski J Q (2010). Epothilone D improves microtubule density, axonal integrity, and cognition in a transgenic mouse model of tauopathy. J Neurosci, 30(41): 13861–13866
Bugyi B, Papp G, Hild G, Lõrinczy D, Nevalainen E M, Lappalainen P, Somogyi B, Nyitrai M (2006). Formins regulate actin filament flexibility through long range allosteric interactions. J Biol Chem, 281(16): 10727–10736
Caceres A, Banker G, Steward O, Binder L, Payne M (1984). MAP2 is localized to the dendrites of hippocampal neurons which develop in culture. Brain Res, 315(2): 314–318
Cairns N J, Lee V M Y, Trojanowski J Q (2004). The cytoskeleton in neurodegenerative diseases. J Pathol, 204(4): 438–449
Chai X, Förster E, Zhao S, Bock H H, Frotscher M (2009). Reelin stabilizes the actin cytoskeleton of neuronal processes by inducing ncofilin phosphorylation at serine3. J Neurosci, 29(1): 288–299
Chen Y, Zheng ZZ, Huang R, Chen K, Song W, Zhao B, Chen X, Yang Y, Yuan L, Shang HF (2013) PFN1 mutations are rare in Han Chinese populations with amyotrophic lateral sclerosis. Neurobiol Aging 34:1922 e1921–1925.
Clinton SM, Abelson S, Haroutunian V, Davis K, Meador-Woodruff J H (2004). Neurofilament subunit protein abnormalities in the thalamus in scizophrenia. Thalamus Relat Syst, 2: 265–272
Clinton S M, Haroutunian V, Davis K L, Meador-Woodruff J H (2003). Altered transcript expression of NMDA receptor-associated postsynaptic proteins in the thalamus of subjects with schizophrenia. Am J Psychiatry, 160(6): 1100–1109
Cohen R S, Chung S K, Pfaff D W (1985). Immunocytochemical localization of actin in dendritic spines of the cerebral cortex using colloidal gold as a probe. Cell Mol Neurobiol, 5(3): 271–284
Collard J F, Côté F, Julien J P (1995). Defective axonal transport in a transgenic mouse model of amyotrophic lateral sclerosis. Nature, 375(6526): 61–64
Côté F, Collard J F, Julien J P (1993). Progressive neuronopathy in transgenic mice expressing the human neurofilament heavy gene: a mouse model of amyotrophic lateral sclerosis. Cell, 73(1): 35–46
Cotter D, Wilson S, Roberts E, Kerwin R, Everall I P (2000). Increased dendritic MAP2 expression in the hippocampus in schizophrenia. Schizophr Res, 41(2): 313–323
Daoud H, Dobrzeniecka S, Camu W, Meininger V, Dupre N, Dion PA, Rouleau GA (2013) Mutation analysis of PFN1 in familial amyotrophic lateral sclerosis patients. Neurobiol Aging 34:1311 e1311–1312.
Dehmelt L, Halpain S (2004). Actin and microtubules in neurite initiation: are MAPs the missing link? J Neurobiol, 58(1): 18–33
Dent EW, Kalil K (2001). Axon branching requires interactions between dynamic microtubules and actin filaments. J Neurosci, 21(24): 9757–9769
Deo A J, Goldszer I M, Li S, DiBitetto J V, Henteleff R, Sampson A, Lewis D A, Penzes P, Sweet R A (2013). PAK1 protein expression in the auditory cortex of schizophrenia subjects. PLoS ONE, 8(4): e59458
Díez-Guerra F J, Avila J (1993). MAP2 phosphorylation parallels dendrite arborization in hippocampal neurones in culture. Neuroreport, 4(4): 419–422
DiProspero N A, Chen E Y, Charles V, Plomann M, Kordower J H, Tagle D A (2004). Early changes in Huntington’s disease patient brains involve alterations in cytoskeletal and synaptic elements. J Neurocytol, 33(5): 517–533
Dixit R, Ross J L, Goldman Y E, Holzbaur E L (2008). Differential regulation of dynein and kinesin motor proteins by tau. Science, 319(5866): 1086–1089
Dom R, Malfroid M, Baro F (1976). Neuropathology of Huntington’s chorea. Studies of the ventrobasal complex of the thalamus. Neurology, 26(1): 64–68
Downing K H, Nogales E (1998). Tubulin and microtubule structure. Curr Opin Cell Biol, 10(1): 16–22
Duan W, Guo Y, Jiang H, Yu X, Li C (2011). MG132 enhances neurite outgrowth in neurons overexpressing mutant TAR DNA-binding protein-43 via increase of HO-1. Brain Res, 1397: 1–9
Ebneth A, Godemann R, Stamer K, Illenberger S, Trinczek B, Mandelkow E (1998). Overexpression of tau protein inhibits kinesin-dependent trafficking of vesicles, mitochondria, and endoplasmic reticulum: implications for Alzheimer’s disease. J Cell Biol, 143(3): 777–794
Edwards D C, Sanders L C, Bokoch GM, Gill G N (1999). Activation of LIM-kinase by Pak1 couples Rac/Cdc42 GTPase signalling to actin cytoskeletal dynamics. Nat Cell Biol, 1(5): 253–259
Ehlers M D, Fung E T, O’Brien R J, Huganir R L (1998). Splice variantspecific interaction of the NMDA receptor subunit NR1 with neuronal intermediate filaments. J Neurosci, 18(2): 720–730
Ehlers M D, Tingley W G, Huganir R L (1995). Regulated subcellular distribution of the NR1 subunit of the NMDA receptor. Science, 269(5231): 1734–1737
Ferri C P, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M, Hall K, Hasegawa K, Hendrie H, Huang Y, Jorm A, Mathers C, Menezes P R, Rimmer E, Scazufca M, and the Alzheimer’s Disease International (2005). Global prevalence of dementia: a Delphi consensus study. Lancet, 366(9503): 2112–2117
Figlewicz D A, Krizus A, Martinoli M G, Meininger V, Dib M, Rouleau G A, Julien J P (1994). Variants of the heavy neurofilament subunit are associated with the development of amyotrophic lateral sclerosis. Hum Mol Genet, 3(10): 1757–1761
Freiman T M, Eismann-Schweimler J, Frotscher M (2011). Granule cell dispersion in temporal lobe epilepsy is associated with changes in dendritic orientation and spine distribution. Exp Neurol, 229(2): 332–338
Fuchs E, Cleveland DW (1998). A structural scaffolding of intermediate filaments in health and disease. Science, 279(5350): 514–519
Fulga T A, Elson-Schwab I, Khurana V, Steinhilb M L, Spires T L, Hyman B T, Feany M B (2007). Abnormal bundling and accumulation of F-actin mediates tau-induced neuronal degeneration in vivo. Nat Cell Biol, 9(2): 139–148
Galloway P G, Mulvihill P, Perry G (1992). Filaments of Lewy bodies contain insoluble cytoskeletal elements. Am J Pathol, 140(4): 809–822
Galloway P G, Perry G, Gambetti P (1987). Hirano body filaments contain actin and actin-associated proteins. J Neuropathol Exp Neurol, 46(2): 185–199
Garey L J, Ong W Y, Patel T S, Kanani M, Davis A, Mortimer A M, Barnes T R, Hirsch S R (1998). Reduced dendritic spine density on cerebral cortical pyramidal neurons in schizophrenia. J Neurol Neurosurg Psychiatry, 65(4): 446–453
Ge W W, Wen W, Strong W, Leystra-Lantz C, Strong M J (2005). Mutant copper-zinc superoxide dismutase binds to and destabilizes human low molecular weight neurofilament mRNA. J Biol Chem, 280(1): 118–124
Gibson P H, Tomlinson B E (1977). Numbers of Hirano bodies in the hippocampus of normal and demented people with Alzheimer’s disease. J Neurol Sci, 33(1–2): 199–206
Glantz L A, Lewis D A (2000). Decreased dendritic spine density on prefrontal cortical pyramidal neurons in schizophrenia. Arch Gen Psychiatry, 57(1): 65–73
Glantz L A, Lewis D A (2001). Dendritic spine density in schizophrenia and depression. Arch Gen Psychiatry, 58(2): 203
Goedert M, Wischik C M, Crowther R A, Walker J E, Klug A (1988). Cloning and sequencing of the cDNA encoding a core protein of the paired helical filament of Alzheimer disease: identification as the microtubule-associated protein tau. Proc Natl Acad Sci USA, 85(11): 4051–4055
Grundke-Iqbal I, Iqbal K, Quinlan M, Tung Y C, Zaidi M S, Wisniewski H M (1986a). Microtubule-associated protein tau. A component of Alzheimer paired helical filaments. J Biol Chem, 261(13): 6084–6089
Grundke-Iqbal I, Iqbal K, Tung Y C, Quinlan M, Wisniewski H M, Binder L I (1986b). Abnormal phosphorylation of the microtubuleassociated protein tau (τ) in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci USA, 83(13): 4913–4917
Gunning P, O’Neill G, Hardeman E (2008). Tropomyosin-based regulation of the actin cytoskeleton in time and space. Physiol Rev, 88(1): 1–35
Haas C A, Dudeck O, Kirsch M, Huszka C, Kann G, Pollak S, Zentner J, Frotscher M (2002). Role for reelin in the development of granule cell dispersion in temporal lobe epilepsy. J Neurosci, 22(14): 5797–5802
Hanger D P, Anderton B H, Noble W (2009). Tau phosphorylation: the therapeutic challenge for neurodegenerative disease. Trends Mol Med, 15(3): 112–119
Hayashi M L, Choi S Y, Rao B S, Jung H Y, Lee H K, Zhang D, Chattarji S, Kirkwood A, Tonegawa S (2004). Altered cortical synaptic morphology and impaired memory consolidation in forebrain-specific dominant-negative PAK transgenic mice. Neuron, 42(5): 773–787
Hill J J, Hashimoto T, Lewis D A (2006). Molecular mechanisms contributing to dendritic spine alterations in the prefrontal cortex of subjects with schizophrenia. Mol Psychiatry, 11(6): 557–566
Hill W D, Lee V M, Hurtig H I, Murray J M, Trojanowski J Q (1991). Epitopes located in spatially separate domains of each neurofilament subunit are present in Parkinson’s disease Lewy bodies. J Comp Neurol, 309(1): 150–160
Houser C R (1990). Granule cell dispersion in the dentate gyrus of humans with temporal lobe epilepsy. Brain Res, 535(2): 195–204
Hutton M, Lendon C L, Rizzu P, Baker M, Froelich S, Houlden H, Pickering-Brown S, Chakraverty S, Isaacs A, Grover A, Hackett J, Adamson J, Lincoln S, Dickson D, Davies P, Petersen R C, Stevens M, de Graaff E, Wauters E, van Baren J, Hillebrand M, Joosse M, Kwon J M, Nowotny P, Che L K, Norton J, Morris J C, Reed L A, Trojanowski J, Basun H, Lannfelt L, Neystat M, Fahn S, Dark F, Tannenberg T, Dodd P R, Hayward N, Kwok J B, Schofield P R, Andreadis A, Snowden J, Craufurd D, Neary D, Owen F, Oostra B A, Hardy J, Goate A, van Swieten J, Mann D, Lynch T, Heutink P (1998). Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17. Nature, 393(6686): 702–705
Ingre C, Landers JE, Rizik N, Volk AE, Akimoto C, Birve A, Hubers A, Keagle PJ, Piotrowska K, Press R, Andersen PM, Ludolph AC, Weishaupt J H (2013). A novel phosphorylation site mutation in profilin 1 revealed in a large screen of US, Nordic, and German amyotrophic lateral sclerosis/frontotemporal dementia cohorts. Neurobiol Aging, 34:1708 e1701–1706
Iqbal K, Grundke-Iqbal I, Zaidi T, Merz P A, Wen G Y, Shaikh S S, Wisniewski H M, Alafuzoff I, Winblad B (1986). Defective brain microtubule assembly in Alzheimer’s disease. Lancet, 2(8504): 421–426
Ittner LM, Ke Y D, Delerue F, Bi M, Gladbach A, van Eersel J, Wölfing H, Chieng B C, Christie M J, Napier I A, Eckert A, Staufenbiel M, Hardeman E, Götz J (2010). Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer’s disease mouse models. Cell, 142(3): 387–397
Jordanova A, De Jonghe P, Boerkoel C F, Takashima H, De Vriendt E, Ceuterick C, Martin J J, Butler I J, Mancias P, Papasozomenos S Ch, Terespolsky D, Potocki L, Brown C W, Shy M, Rita D A, Tournev I, Kremensky I, Lupski J R, Timmerman V (2003). Mutations in the neurofilament light chain gene (NEFL) cause early onset severe Charcot-Marie-Tooth disease. Brain, 126(Pt 3): 590–597
Ke Y D, Suchowerska A K, van der Hoven J, De Silva D M, Wu C W, van Eersel J, Ittner A, Ittner L M (2012). Lessons from tau-deficient mice. Int J Alzheimers Dis, 2012: 873270
Kim C H, Lisman J E (1999). A role of actin filament in synaptic transmission and long-term potentiation. J Neurosci, 19(11): 4314–4324
Korobova F, Svitkina T (2008). Arp2/3 complex is important for filopodia formation, growth cone motility, and neuritogenesis in neuronal cells. Mol Biol Cell, 19(4): 1561–1574
Krüger R, Fischer C, Schulte T, Strauss KM, Müller T, Woitalla D, Berg D, Hungs M, Gobbele R, Berger K, Epplen J T, Riess O, Schöls L (2003). Mutation analysis of the neurofilamentMgene in Parkinson’s disease. Neurosci Lett, 351(2): 125–129
Kuhn T B, Bamburg J R (2008). Tropomyosin and ADF/cofilin as collaborators and competitors. Adv Exp Med Biol, 644: 232–249
Lattante S, Le Ber I, Camuzat A, Brice A, Kabashi E (2013). Mutations in the PFN1 gene are not a common cause in patients with amyotrophic lateral sclerosis and frontotemporal lobar degeneration in France. Neurobiol Aging, 34:1709 e1701–1702
Lavedan C, Buchholtz S, Nussbaum R L, Albin R L, Polymeropoulos M H (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(1): 57–61
Lee M K, Marszalek J R, Cleveland D W (1994). A mutant neurofilament subunit causes massive, selective motor neuron death: implications for the pathogenesis of human motor neuron disease. Neuron, 13(4): 975–988
Lee V M, Goedert M, Trojanowski J Q (2001). Neurodegenerative tauopathies. Annu Rev Neurosci, 24(1): 1121–1159
Li B, Chohan M O, Grundke-Iqbal I, Iqbal K (2007). Disruption of microtubule network by Alzheimer abnormally hyperphosphorylated tau. Acta Neuropathol, 113(5): 501–511
Lücking C B, Dürr A, Bonifati V, Vaughan J, De Michele G, Gasser T, Harhangi B S, Meco G, Denèfle P, Wood NW, Agid Y, Brice A, and the French Parkinson’s Disease Genetics Study Group, and the European Consortium on Genetic Susceptibility in Parkinson’s Disease (2000). Association between early-onset Parkinson’s disease and mutations in the parkin gene. N Engl J Med, 342(21): 1560–1567
Luo L, Hensch T K, Ackerman L, Barbel S, Jan L Y, Jan Y N (1996). Differential effects of the Rac GTPase on Purkinje cell axons and dendritic trunks and spines. Nature, 379(6568): 837–840
Maciver S K, Harrington C R (1995). Two actin binding proteins, actin depolymerizing factor and cofilin, are associated with Hirano bodies. Neuroreport, 6(15): 1985–1988
Mahammad S, Murthy S N, Didonna A, Grin B, Israeli E, Perrot R, Bomont P, Julien J P, Kuczmarski E, Opal P, Goldman R D (2013). Giant axonal neuropathy-associated gigaxonin mutations impair intermediate filament protein degradation. J Clin Invest, 123(5): 1964–1975
Manetto V, Sternberger N H, Perry G, Sternberger L A, Gambetti P (1988). Phosphorylation of neurofilaments is altered in amyotrophic lateral sclerosis. J Neuropathol Exp Neurol, 47(6): 642–653
Manser E, Leung T, Salihuddin H, Zhao Z S, Lim L (1994). A brain serine/threonine protein kinase activated by Cdc42 and Rac1. Nature, 367(6458): 40–46
Matus A (1988). Microtubule-associated proteins: their potential role in determining neuronal morphology. Annu Rev Neurosci, 11(1): 29–44
Minamide L S, Striegl AM, Boyle J A, Meberg P J, Bamburg J R (2000). Neurodegenerative stimuli induce persistent ADF/cofilin-actin rods that disrupt distal neurite function. Nat Cell Biol, 2(9): 628–636
Mitchison T J, Cramer L P (1996). Actin-based cell motility and cell locomotion. Cell, 84(3): 371–379
Mockrin S C, Korn E D (1980). Acanthamoeba profilin interacts with Gactin to increase the rate of exchange of actin-bound adenosine 5′-triphosphate. Biochemistry, 19(23): 5359–5362
Morfini G, Pigino G, Mizuno N, Kikkawa M, Brady S T (2007). Tau binding to microtubules does not directly affect microtubule-based vesicle motility. J Neurosci Res, 85(12): 2620–2630
Moriwaki A, Lu Y F, Tomizawa K, Matsui H (1998). An immunosuppressant, FK506, protects against neuronal dysfunction and death but has no effect on electrographic and behavioral activities induced by systemic kainate. Neuroscience, 86(3): 855–865
Morrison BM, Shu IW, Wilcox A L, Gordon JW, Morrison J H (2000). Early and selective pathology of light chain neurofilament in the spinal cord and sciatic nerve of G86R mutant superoxide dismutase transgenic mice. Exp Neurol, 165(2): 207–220
Munoz D G, Greene C, Perl D P, Selkoe D J (1988). Accumulation of phosphorylated neurofilaments in anterior horn motoneurons of amyotrophic lateral sclerosis patients. J Neuropathol Exp Neurol, 47(1): 9–18
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 neuropathologica / Association of Polish Neuropathologists and Medical Research Centre. Polish Academy of Sciences, 44: 191–196
Nishida E, Iida K, Yonezawa N, Koyasu S, Yahara I, Sakai H (1987). Cofilin is a component of intranuclear and cytoplasmic actin rods induced in cultured cells. Proc Natl Acad Sci USA, 84(15): 5262–5266
Niwa R, Nagata-Ohashi K, Takeichi M, Mizuno K, Uemura T (2002). Control of actin reorganization by Slingshot, a family of phosphatases that dephosphorylate ADF/cofilin. Cell, 108(2): 233–246
Okamoto K, Nagai T, Miyawaki A, Hayashi Y (2004). Rapid and persistent modulation of actin dynamics regulates postsynaptic reorganization underlying bidirectional plasticity. Nat Neurosci, 7(10): 1104–1112
Ouyang Y, Yang X F, Hu X Y, Erbayat-Altay E, Zeng L H, Lee J M, Wong M (2007). Hippocampal seizures cause depolymerization of filamentous actin in neurons independent of acute morphological changes. Brain Res, 1143: 238–246
Patrick G N, Zukerberg L, Nikolic M, de la Monte S, Dikkes P, Tsai L H (1999). Conversion of p35 to p25 deregulates Cdk5 activity and promotes neurodegeneration. Nature, 402(6762): 615–622
Pavlik L L, Moshkov D A (1991). Actin in synaptic cytoskeleton during long-term potentiation in hippocampal slices. Acta Histochem Suppl, 41(Supp 41): 257–264
Pérez-Ollé R, López-Toledano M A, Goryunov D, Cabrera-Poch N, Stefanis L, Brown K, Liem R K (2005). Mutations in the neurofilament light gene linked to Charcot-Marie-Tooth disease cause defects in transport. J Neurochem, 93(4): 861–874
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(1): 27–65
Powell K J, Hori S E, Leslie R, Andrieux A, Schellinck H, Thorne M, Robertson G S (2007). Cognitive impairments in the STOP null mouse model of schizophrenia. Behav Neurosci, 121(5): 826–835
Prineas J W, Ouvrier R A, Wright R G, Walsh J C, McLeod J G (1976). Gian axonal neuropathy—a generalized disorder of cytoplasmic microfilament formation. J Neuropathol Exp Neurol, 35(4): 458–470
Qiang L, Yu W, Andreadis A, Luo M, Baas P W (2006). Tau protects microtubules in the axon from severing by katanin. J Neurosci, 26(12): 3120–3129
Rao M V, Mohan P S, Kumar A, Yuan A, Montagna L, Campbell J, Veeranna, Espreafico EM, Julien J P, Nixon R A (2011). The myosin Va head domain binds to the neurofilament-L rod and modulates endoplasmic reticulum (ER) content and distribution within axons. PLoS ONE, 6(2): e17087
Ren Y, Jiang H, Yang F, Nakaso K, Feng J (2009). Parkin protects dopaminergic neurons against microtubule-depolymerizing toxins by attenuating microtubule-associated protein kinase activation. J Biol Chem, 284(6): 4009–4017
Ren Y, Zhao J, Feng J (2003). Parkin binds to alpha/beta tubulin and increases their ubiquitination and degradation. J Neurosci, 23(8): 3316–3324
Rex C S, Chen L Y, Sharma A, Liu J, Babayan A H, Gall C M, Lynch G (2009). Different Rho GTPase-dependent signaling pathways initiate sequential steps in the consolidation of long-term potentiation. J Cell Biol, 186(1): 85–97
Rossiter J P, Anderson L L, Yang F, Cole G M (2000). Caspase-cleaved actin (fractin) immunolabelling of Hirano bodies. Neuropathol Appl Neurobiol, 26(4): 342–346
Rossoll W, Jablonka S, Andreassi C, Kröning A K, Karle K, Monani U R, Sendtner M (2003). Smn, the spinal muscular atrophy-determining gene product, modulates axon growth and localization of beta-actin mRNA in growth cones of motoneurons. J Cell Biol, 163(4): 801–812
Rovelet-Lecrux A, Campion D (2012). Copy number variations involving the microtubule-associated protein tau in human diseases. Biochem Soc Trans, 40(4): 672–676
Roy S, Zhang B, Lee V M, Trojanowski J Q (2005). Axonal transport defects: a common theme in neurodegenerative diseases. Acta Neuropathol, 109(1): 5–13
Rubio M D, Haroutunian V, Meador-Woodruff J H (2012). Abnormalities of the Duo/Ras-related C3 botulinum toxin substrate 1/p21-activated kinase 1 pathway drive myosin light chain phosphorylation in frontal cortex in schizophrenia. Biol Psychiatry, 71(10): 906–914
Sánchez C, Arellano J I, Rodríguez-Sánchez P, Avila J, DeFelipe J, Díez-Guerra F J (2001). Microtubule-associated protein 2 phosphorylation is decreased in the human epileptic temporal lobe cortex. Neuroscience, 107(1): 25–33
Sánchez C, Díaz-Nido J, Avila J (2000). Phosphorylation of microtubule-associated protein 2 (MAP2) and its relevance for the regulation of the neuronal cytoskeleton function. Prog Neurobiol, 61(2): 133–168
Scheibel M E, Crandall P H, Scheibel A B (1974). The hippocampaldentate complex in temporal lobe epilepsy. A Golgi study. Epilepsia, 15(1): 55–80
Schevzov G, Curthoys N M, Gunning P W, Fath T (2012). Functional diversity of actin cytoskeleton in neurons and its regulation by tropomyosin. Int Rev Cell Mol Biol, 298: 33–94
Schmidt M L, Lee V M, Trojanowski J Q (1989). Analysis of epitopes shared by Hirano bodies and neurofilament proteins in normal and Alzheimer’s disease hippocampus. Lab Invest, 60(4): 513–522
Schneider A B J, Biernat J, von Bergen M, Mandelkow E M, Mandelkow E M (1999). Phosphorylation that detaches tau protein from microtubules (Ser262, Ser214) also protects it against aggregation into Alzheimer paired helical filaments. Biochemistry, 38(12): 3549–3558
Scott W K, Nance M A, Watts R L, Hubble J P, Koller W C, Lyons K, Pahwa R, Stern M B, Colcher A, Hiner B C, Jankovic J, Ondo W G, Allen F H Jr, Goetz C G, Small G W, Masterman D, Mastaglia F, Laing N G, Stajich J M, Slotterbeck B, Booze M W, Ribble R C, Rampersaud E, West S G, Gibson R A, Middleton L T, Roses A D, Haines J L, Scott B L, Vance J M, Pericak-Vance M A (2001). Complete genomic screen in Parkinson disease: evidence for multiple genes. JAMA, 286(18): 2239–2244
Seitz A, Kojima H, Oiwa K, Mandelkow E M, Song Y H, Mandelkow E (2002). Single-molecule investigation of the interference between kinesin, tau and MAP2c. EMBO J, 21(18): 4896–4905
Shimizu H, Iwayama Y, Yamada K, Toyota T, Minabe Y, Nakamura K, Nakajima M, Hattori E, Mori N, Osumi N, Yoshikawa T (2006). Genetic and expression analyses of the STOP (MAP6) gene in schizophrenia. Schizophr Res, 84(2-3): 244–252
Sousa V L, Bellani S, Giannandrea M, Yousuf M, Valtorta F, Meldolesi J, Chieregatti E (2009). alpha-synuclein and its A30P mutant affect actin cytoskeletal structure and dynamics. Mol Biol Cell, 20(16): 3725–3739
Sternberger L A, Sternberger N H (1983). Monoclonal antibodies distinguish phosphorylated and nonphosphorylated forms of neuro-filaments in situ. Proc Natl Acad Sci USA, 80(19): 6126–6130
Sudo H, Baas P W (2011). Strategies for diminishing katanin-based loss of microtubules in tauopathic neurodegenerative diseases. Hum Mol Genet, 20(4): 763–778
Sweet R A, Henteleff R A, Zhang W, Sampson A R, Lewis D A (2009). Reduced dendritic spine density in auditory cortex of subjects with schizophrenia. Neuropsychopharmacology, 34(2): 374–389
Takeuchi H, Kobayashi Y, Yoshihara T, Niwa J, Doyu M, Ohtsuka K, Sobue G (2002). Hsp70 and Hsp40 improve neurite outgrowth and suppress intracytoplasmic aggregate formation in cultured neuronal cells expressing mutant SOD1. Brain Res, 949(1–2): 11–22
Tiloca C, Ticozzi N, Pensato V, Corrado L, Del Bo R, Bertolin C, Fenoglio C, Gagliardi S, Calini D, Lauria G, Castellotti B, Bagarotti A, Corti S, Galimberti D, Cagnin A, Gabelli C, Ranieri M, Ceroni M, Siciliano G, Mazzini L, Cereda C, Scarpini E, Soraru G, Comi GP, D’Alfonso S, Gellera C, Ratti A, Landers JE, Silani V (2013). Screening of the PFN1 gene in sporadic amyotrophic lateral sclerosis and in frontotemporal dementia. Neurobiol Aging, 34:1517 e1519–1510
Torres-Benito L, Ruiz R, Tabares L (2012). Synaptic defects in spinal muscular atrophy animal models. Dev Neurobiol, 72(1): 126–133
Tortelli R, Ruggieri M, Cortese R, D’Errico E, Capozzo R, Leo A, Mastrapasqua M, Zoccolella S, Leante R, Livrea P, Logroscino G, Simone I L (2012). Elevated cerebrospinal fluid neurofilament light levels in patients with amyotrophic lateral sclerosis: a possible marker of disease severity and progression. Eur J Neurol, 19(12): 1561–1567
Trojanowski J Q, Lee VMY (2005). Rous-Whipple Award Lecture. The Alzheimer’s brain: finding out what’s broken tells us how to fix it. Am J Pathol, 167(5): 1183–1188
Tseng Y, An K M, Esue O, Wirtz D (2004). The bimodal role of filamin in controlling the architecture and mechanics of F-actin networks. J Biol Chem, 279(3): 1819–1826
van Blitterswijk M, Baker MC, Bieniek KF, Knopman DS, Josephs KA, Boeve B, Caselli R, Wszolek ZK, Petersen R, Graff-Radford NR, Boylan KB, Dickson DW, Rademakers R (2013). Profilin-1 mutations are rare in patients with amyotrophic lateral sclerosis and frontotemporal dementia. Amyotroph Lateral Scler Frontotemporal Degener 14:463–469
Wagner U, Utton M, Gallo J M, Miller C C (1996). Cellular phosphorylation of tau by GSK-3 beta influences tau binding to microtubules and microtubule organisation. J Cell Sci, 109(Pt 6): 1537–1543
Wong N K, He B P, Strong M J (2000). Characterization of neuronal intermediate filament protein expression in cervical spinal motor neurons in sporadic amyotrophic lateral sclerosis (ALS). J Neuropathol Exp Neurol, 59(11): 972–982
Wu C H, Fallini C, Ticozzi N, Keagle P J, Sapp P C, Piotrowska K, Lowe P, Koppers M, McKenna-Yasek D, Baron D M, Kost J E, Gonzalez-Perez P, Fox A D, Adams J, Taroni F, Tiloca C, Leclerc A L, Chafe S C, Mangroo D, Moore MJ, Zitzewitz J A, Xu Z S, van den Berg L H, Glass J D, Siciliano G, Cirulli E T, Goldstein D B, Salachas F, Meininger V, Rossoll W, Ratti A, Gellera C, Bosco D A, Bassell G J, Silani V, Drory V E, Brown R H Jr, Landers J E (2012). Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis. Nature, 488(7412): 499–503
Xie Z, Srivastava D P, Photowala H, Kai L, Cahill M E, Woolfrey K M, Shum C Y, Surmeier D J, Penzes P (2007). Kalirin-7 controls activity-dependent structural and functional plasticity of dendritic spines. Neuron, 56(4): 640–656
Xu Z, Cork L C, Griffin J W, Cleveland D W (1993). Increased expression of neurofilament subunit NF-L produces morphological alterations that resemble the pathology of human motor neuron disease. Cell, 73(1): 23–33
Yang F, Jiang Q, Zhao J, Ren Y, Sutton M D, Feng J (2005). Parkin stabilizes microtubules through strong binding mediated by three independent domains. J Biol Chem, 280(17): 17154–17162
Yang N, Higuchi O, Ohashi K, Nagata K, Wada A, Kangawa K, Nishida E, Mizuno K (1998). Cofilin phosphorylation by LIM-kinase 1 and its role in Rac-mediated actin reorganization. Nature, 393(6687): 809–812
Yang S, Fifita J A, Williams K L, Warraich ST, Pamphlett R, Nicholson G A, Blair I P (2013). Mutation analysis and immunopathological studies of PFN1 in familial and sporadic amyotrophic lateral sclerosis. Neurobiol Aging, 34:2235 e2237–2210
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(4): 221–224
Zeng L H, Xu L, Rensing N R, Sinatra P M, Rothman S M, Wong M (2007). Kainate seizures cause acute dendritic injury and actin depolymerization in vivo. J Neurosci, 27(43): 11604–11613
Zhang B, Carroll J, Trojanowski J Q, Yao Y, Iba M, Potuzak J S, Hogan A M L, Xie S X, Ballatore C, Smith A B 3rd, Lee V M L, Brunden K R (2012). The microtubule-stabilizing agent, epothilone D, reduces axonal dysfunction, neurotoxicity, cognitive deficits, and Alzheimerlike pathology in an interventional study with aged tau transgenic mice. J Neurosci, 32(11): 3601–3611
Zhang B, Maiti A, Shively S, Lakhani F, McDonald-Jones G, Bruce J, Lee E B, Xie S X, Joyce S, Li C, Toleikis PM, Lee VM, Trojanowski J Q (2005). Microtubule-binding drugs offset tau sequestration by stabilizing microtubules and reversing fast axonal transport deficits in a tauopathy model. Proc Natl Acad Sci USA, 102(1): 227–231
Zhang W, Benson D L (2001). Stages of synapse development defined by dependence on F-actin. J Neurosci, 21:5169–5181
Zhu Q, Couillard-Després S, Julien J P (1997). Delayed maturation of regenerating myelinated axons in mice lacking neurofilaments. Exp Neurol, 148(1): 299–316
Zou ZY, Sun Q, Liu MS, Li XG, Cui LY (2013). Mutations in the profilin 1 gene are not common in amyotrophic lateral sclerosis of Chinese origin. Neurobiol Aging, 34:1713 e1715–1716
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Suchowerska, A.K., Fath, T. Cytoskeletal changes in diseases of the nervous system. Front. Biol. 9, 5–17 (2014). https://doi.org/10.1007/s11515-014-1290-6
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DOI: https://doi.org/10.1007/s11515-014-1290-6