REVIEW

Cytoskeletal changes in diseases of the nervous system

  • Alexandra K. SUCHOWERSKA ,
  • Thomas FATH
Expand
  • Neurodegeneration and Repair Unit, School of Medical Sciences, University of New South Wales, Randwick, New South Wales 2052, Australia

Received date: 16 Oct 2013

Accepted date: 16 Dec 2013

Published date: 01 Feb 2014

Copyright

2014 Higher Education Press and Springer-Verlag Berlin Heidelberg

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.

Cite this article

Alexandra K. SUCHOWERSKA , Thomas FATH . Cytoskeletal changes in diseases of the nervous system[J]. Frontiers in Biology, 2014 , 9(1) : 5 -17 . DOI: 10.1007/s11515-014-1290-6

Acknowledgements

We thank Dr. Anthony Kee for critical reading of the manuscript and for the support from Australian Research Council Discovery Project Grant 110102771.
Compliance with ethic guidelines
Alexandra K. Suchowerska and Thomas Fath declare that they have no conflict of interest.
This article does not contain any studies with human or animal subjects performed by any of the authors.
1
Al-ChalabiA, AndersenP M, NilssonP, ChiozaB, AnderssonJ L, RussC, ShawC E, PowellJ F, LeighP N (1999). Deletions of the heavy neurofilament subunit tail in amyotrophic lateral sclerosis. Hum Mol Genet, 8(2): 157–164

DOI PMID

2
AndersonS A, VolkD W, LewisD 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

DOI PMID

3
AndrianantoandroE, PollardT D (2006). Mechanism of actin filament turnover by severing and nucleation at different concentrations of ADF/cofilin. Mol Cell, 24(1): 13–23

DOI PMID

4
AndrieuxA, SalinP A, VernetM, KujalaP, BaratierJ, Gory-FauréS, BoscC, PointuH, ProiettoD, SchweitzerA, DenarierE, KlumpermanJ, JobD (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

DOI PMID

5
ArberS, BarbayannisF A, HanserH, SchneiderC, StanyonC A, BernardO, CaroniP (1998). Regulation of actin dynamics through phosphorylation of cofilin by LIM-kinase. Nature, 393(6687): 805–809

DOI PMID

6
ArmstrongR A, CairnsN J (2012). Different molecular pathologies result in similar spatial patterns of cellular inclusions in neurodegenerative disease: a comparative study of eight disorders. J Neural Transm, 119(12): 1551–1560

DOI PMID

7
ArmstrongR A, KertyE, SkullerudK, CairnsN 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

DOI PMID

8
AsburyA K, GaleM K, CoxS C, BaringerJ R, BergB O (1972). Giant axonal neuropathy—a unique case with segmental neurofilamentous masses. Acta Neuropathol, 20(3): 237–247

DOI PMID

9
AsrarS, MengY, ZhouZ, TodorovskiZ, HuangW W, JiaZ (2009). Regulation of hippocampal long-term potentiation by p21-activated protein kinase 1 (PAK1). Neuropharmacology, 56(1): 73–80

DOI PMID

10
BaasP W, AhmadF J (2013). Beyond taxol: microtubule-based treatment of disease and injury of the nervous system. Brain, 136(Pt 10): 2937–2951

DOI PMID

11
BallatoreC, LeeV M, TrojanowskiJ Q (2007). Tau-mediated neurodegeneration in Alzheimer’s disease and related disorders. Nat Rev Neurosci, 8(9): 663–672

DOI PMID

12
BégouM, BrunP, BertrandJ B, JobD, SchweitzerA, D’AmatoT, SaoudM, AndrieuxA, Suaud-ChagnyM F (2007). Post-pubertal emergence of alterations in locomotor activity in stop null mice. Synapse, 61(9): 689–697

DOI PMID

13
BégouM, VolleJ, BertrandJ B, BrunP, JobD, SchweitzerA, SaoudM, D’AmatoT, AndrieuxA, Suaud-ChagnyM F (2008). The stop null mice model for schizophrenia displays [corrected] cognitive and social deficits partly alleviated by neuroleptics. Neuroscience, 157(1): 29–39

DOI PMID

14
BelichenkoP V, DahlströmA (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

DOI PMID

15
Bento-AbreuA, Van DammeP, Van Den BoschL, RobberechtW (2010). The neurobiology of amyotrophic lateral sclerosis. Eur J Neurosci, 31(12): 2247–2265

DOI PMID

16
BergeronC, Beric-MaskarelK, MuntasserS, WeyerL, SomervilleM J, PercyM E (1994). Neurofilament light and polyadenylated mRNA levels are decreased in amyotrophic lateral sclerosis motor neurons. J Neuropathol Exp Neurol, 53(3): 221–230

DOI PMID

17
BernhardtR, MatusA (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

DOI PMID

18
BishopA L, HallA (2000). Rho GTPases and their effector proteins. Biochem J, 348(Pt 2): 241–255

DOI PMID

19
BloomG S, ValleeR 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

DOI PMID

20
BocquetA, BergesR, FrankR, RobertP, PetersonA C, EyerJ (2009). Neurofilaments bind tubulin and modulate its polymerization. J Neurosci, 29(35): 11043–11054

DOI PMID

21
BoschM, HayashiY (2012). Structural plasticity of dendritic spines. Curr Opin Neurobiol, 22(3): 383–388

DOI PMID

22
BrettschneiderJ, PetzoldA, SüssmuthS D, LudolphA C, TumaniH (2006). Axonal damage markers in cerebrospinal fluid are increased in ALS. Neurology, 66(6): 852–856

DOI PMID

23
BrunP, BégouM, AndrieuxA, Mouly-BadinaL, ClergetM, SchweitzerA, ScarnaH, RenaudB, JobD, Suaud-ChagnyM F (2005). Dopaminergic transmission in STOP null mice. J Neurochem, 94(1): 63–73

DOI PMID

24
BrundenK R, ZhangB, CarrollJ, YaoY, PotuzakJ S, HoganA M, IbaM, JamesM J, XieS X, BallatoreC, SmithA B 3rd, LeeV M Y, TrojanowskiJ Q (2010). Epothilone D improves microtubule density, axonal integrity, and cognition in a transgenic mouse model of tauopathy. J Neurosci, 30(41): 13861–13866

DOI PMID

25
BugyiB, PappG, HildG, LõrinczyD, NevalainenE M, LappalainenP, SomogyiB, NyitraiM (2006). Formins regulate actin filament flexibility through long range allosteric interactions. J Biol Chem, 281(16): 10727–10736

DOI PMID

26
CaceresA, BankerG, StewardO, BinderL, PayneM (1984). MAP2 is localized to the dendrites of hippocampal neurons which develop in culture. Brain Res, 315(2): 314–318

PMID

27
CairnsN J, LeeV M Y, TrojanowskiJ Q (2004). The cytoskeleton in neurodegenerative diseases. J Pathol, 204(4): 438–449

DOI PMID

28
ChaiX, FörsterE, ZhaoS, BockH H, FrotscherM (2009). Reelin stabilizes the actin cytoskeleton of neuronal processes by inducing n-cofilin phosphorylation at serine3. J Neurosci, 29(1): 288–299

DOI PMID

29
ChenY, ZhengZZ, HuangR, ChenK, SongW, ZhaoB, ChenX, YangY, YuanL, ShangHF (2013) PFN1 mutations are rare in Han Chinese populations with amyotrophic lateral sclerosis. Neurobiol Aging34:1922 e1921–1925.

30
ClintonS M, AbelsonS, HaroutunianV, DavisK, Meador-WoodruffJ H (2004). Neurofilament subunit protein abnormalities in the thalamus in scizophrenia. Thalamus Relat Syst, 2: 265–272

31
ClintonS M, HaroutunianV, DavisK L, Meador-WoodruffJ 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

DOI PMID

32
CohenR S, ChungS K, PfaffD 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

DOI PMID

33
CollardJ F, CôtéF, JulienJ P (1995). Defective axonal transport in a transgenic mouse model of amyotrophic lateral sclerosis. Nature, 375(6526): 61–64

DOI PMID

34
CôtéF, CollardJ F, JulienJ 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

DOI PMID

35
CotterD, WilsonS, RobertsE, KerwinR, EverallI P (2000). Increased dendritic MAP2 expression in the hippocampus in schizophrenia. Schizophr Res, 41(2): 313–323

DOI PMID

36
DaoudH, DobrzenieckaS, CamuW, MeiningerV, DupreN, DionPA, RouleauGA (2013) Mutation analysis of PFN1 in familial amyotrophic lateral sclerosis patients. Neurobiol Aging34:1311 e1311–1312.

37
DehmeltL, HalpainS (2004). Actin and microtubules in neurite initiation: are MAPs the missing link? J Neurobiol, 58(1): 18–33

DOI PMID

38
DentE W, KalilK (2001). Axon branching requires interactions between dynamic microtubules and actin filaments. J Neurosci, 21(24): 9757–9769

PMID

39
DeoA J, GoldszerI M, LiS, DiBitettoJ V, HenteleffR, SampsonA, LewisD A, PenzesP, SweetR A (2013). PAK1 protein expression in the auditory cortex of schizophrenia subjects. PLoS ONE, 8(4): e59458

DOI PMID

40
Díez-GuerraF J, AvilaJ (1993). MAP2 phosphorylation parallels dendrite arborization in hippocampal neurones in culture. Neuroreport, 4(4): 419–422

DOI PMID

41
DiProsperoN A, ChenE Y, CharlesV, PlomannM, KordowerJ H, TagleD A (2004). Early changes in Huntington’s disease patient brains involve alterations in cytoskeletal and synaptic elements. J Neurocytol, 33(5): 517–533

DOI PMID

42
DixitR, RossJ L, GoldmanY E, HolzbaurE L (2008). Differential regulation of dynein and kinesin motor proteins by tau. Science, 319(5866): 1086–1089

DOI PMID

43
DomR, MalfroidM, BaroF (1976). Neuropathology of Huntington’s chorea.Studies of the ventrobasal complex of the thalamus. Neurology, 26(1): 64–68

DOI PMID

44
DowningK H, NogalesE (1998). Tubulin and microtubule structure. Curr Opin Cell Biol, 10(1): 16–22

DOI PMID

45
DuanW, GuoY, JiangH, YuX, LiC (2011). MG132 enhances neurite outgrowth in neurons overexpressing mutant TAR DNA-binding protein-43 via increase of HO-1. Brain Res, 1397: 1–9

DOI PMID

46
EbnethA, GodemannR, StamerK, IllenbergerS, TrinczekB, MandelkowE (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

DOI PMID

47
EdwardsD C, SandersL C, BokochG M, GillG N (1999). Activation of LIM-kinase by Pak1 couples Rac/Cdc42 GTPase signalling to actin cytoskeletal dynamics. Nat Cell Biol, 1(5): 253–259

DOI PMID

48
EhlersM D, FungE T, O’BrienR J, HuganirR L (1998). Splice variant-specific interaction of the NMDA receptor subunit NR1 with neuronal intermediate filaments. J Neurosci, 18(2): 720–730

PMID

49
EhlersM D, TingleyW G, HuganirR L (1995). Regulated subcellular distribution of the NR1 subunit of the NMDA receptor. Science, 269(5231): 1734–1737

DOI PMID

50
FerriC P, PrinceM, BrayneC, BrodatyH, FratiglioniL, GanguliM, HallK, HasegawaK, HendrieH, HuangY, JormA, MathersC, MenezesP R, RimmerE, ScazufcaM, and the Alzheimer’s Disease International (2005). Global prevalence of dementia: a Delphi consensus study. Lancet, 366(9503): 2112–2117

DOI PMID

51
FiglewiczD A, KrizusA, MartinoliM G, MeiningerV, DibM, RouleauG A, JulienJ P (1994). Variants of the heavy neurofilament subunit are associated with the development of amyotrophic lateral sclerosis. Hum Mol Genet, 3(10): 1757–1761

DOI PMID

52
FreimanT M, Eismann-SchweimlerJ, FrotscherM (2011). Granule cell dispersion in temporal lobe epilepsy is associated with changes in dendritic orientation and spine distribution. Exp Neurol, 229(2): 332–338

DOI PMID

53
FuchsE, ClevelandD W (1998). A structural scaffolding of intermediate filaments in health and disease. Science, 279(5350): 514–519

DOI PMID

54
FulgaT A, Elson-SchwabI, KhuranaV, SteinhilbM L, SpiresT L, HymanB T, FeanyM B (2007). Abnormal bundling and accumulation of F-actin mediates tau-induced neuronal degeneration in vivo. Nat Cell Biol, 9(2): 139–148

DOI PMID

55
GallowayP G, MulvihillP, PerryG (1992). Filaments of Lewy bodies contain insoluble cytoskeletal elements. Am J Pathol, 140(4): 809–822

PMID

56
GallowayP G, PerryG, GambettiP (1987). Hirano body filaments contain actin and actin-associated proteins. J Neuropathol Exp Neurol, 46(2): 185–199

DOI PMID

57
GareyL J, OngW Y, PatelT S, KananiM, DavisA, MortimerA M, BarnesT R, HirschS R (1998). Reduced dendritic spine density on cerebral cortical pyramidal neurons in schizophrenia. J Neurol Neurosurg Psychiatry, 65(4): 446–453

DOI PMID

58
GeW W, WenW, StrongW, Leystra-LantzC, StrongM J (2005). Mutant copper-zinc superoxide dismutase binds to and destabilizes human low molecular weight neurofilament mRNA. J Biol Chem, 280(1): 118–124

PMID

59
GibsonP H, TomlinsonB 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

DOI PMID

60
GlantzL A, LewisD A (2000). Decreased dendritic spine density on prefrontal cortical pyramidal neurons in schizophrenia. Arch Gen Psychiatry, 57(1): 65–73

DOI PMID

61
GlantzL A, LewisD A (2001). Dendritic spine density in schizophrenia and depression. Arch Gen Psychiatry, 58(2): 203

DOI PMID

62
GoedertM, WischikC M, CrowtherR A, WalkerJ E, KlugA (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

DOI PMID

63
Grundke-IqbalI, IqbalK, QuinlanM, TungY C, ZaidiM S, WisniewskiH M (1986a). Microtubule-associated protein tau.A component of Alzheimer paired helical filaments. J Biol Chem, 261(13): 6084–6089

PMID

64
Grundke-IqbalI, IqbalK, TungY C, QuinlanM, WisniewskiH M, BinderL I (1986b). Abnormal phosphorylation of the microtubule-associated protein tau (τ) in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci USA, 83(13): 4913–4917

DOI PMID

65
GunningP, O’NeillG, HardemanE (2008). Tropomyosin-based regulation of the actin cytoskeleton in time and space. Physiol Rev, 88(1): 1–35

DOI PMID

66
HaasC A, DudeckO, KirschM, HuszkaC, KannG, PollakS, ZentnerJ, FrotscherM (2002). Role for reelin in the development of granule cell dispersion in temporal lobe epilepsy. J Neurosci, 22(14): 5797–5802

PMID

67
HangerD P, AndertonB H, NobleW (2009). Tau phosphorylation: the therapeutic challenge for neurodegenerative disease. Trends Mol Med, 15(3): 112–119

DOI PMID

68
HayashiM L, ChoiS Y, RaoB S, JungH Y, LeeH K, ZhangD, ChattarjiS, KirkwoodA, TonegawaS (2004). Altered cortical synaptic morphology and impaired memory consolidation in forebrain- specific dominant-negative PAK transgenic mice. Neuron, 42(5): 773–787

DOI PMID

69
HillJ J, HashimotoT, LewisD A (2006). Molecular mechanisms contributing to dendritic spine alterations in the prefrontal cortex of subjects with schizophrenia. Mol Psychiatry, 11(6): 557–566

DOI PMID

70
HillW D, LeeV M, HurtigH I, MurrayJ M, TrojanowskiJ 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

DOI PMID

71
HouserC R (1990). Granule cell dispersion in the dentate gyrus of humans with temporal lobe epilepsy. Brain Res, 535(2): 195–204

DOI PMID

72
HuttonM, LendonC L, RizzuP, BakerM, FroelichS, HouldenH, Pickering-BrownS, ChakravertyS, IsaacsA, GroverA, HackettJ, AdamsonJ, LincolnS, DicksonD, DaviesP, PetersenR C, StevensM, de GraaffE, WautersE, van BarenJ, HillebrandM, JoosseM, KwonJ M, NowotnyP, CheL K, NortonJ, MorrisJ C, ReedL A, TrojanowskiJ, BasunH, LannfeltL, NeystatM, FahnS, DarkF, TannenbergT, DoddP R, HaywardN, KwokJ B, SchofieldP R, AndreadisA, SnowdenJ, CraufurdD, NearyD, OwenF, OostraB A, HardyJ, GoateA, van SwietenJ, MannD, LynchT, HeutinkP (1998). Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17. Nature, 393(6686): 702–705

DOI PMID

73
IngreC, LandersJE, RizikN, VolkAE, AkimotoC, BirveA, HubersA, KeaglePJ, PiotrowskaK, PressR, AndersenPM, LudolphAC, WeishauptJ 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

74
IqbalK, Grundke-IqbalI, ZaidiT, MerzP A, WenG Y, ShaikhS S, WisniewskiH M, AlafuzoffI, WinbladB (1986). Defective brain microtubule assembly in Alzheimer’s disease. Lancet, 2(8504): 421–426

DOI PMID

75
IttnerL M, KeY D, DelerueF, BiM, GladbachA, van EerselJ, WölfingH, ChiengB C, ChristieM J, NapierI A, EckertA, StaufenbielM, HardemanE, GötzJ (2010). Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer’s disease mouse models. Cell, 142(3): 387–397

DOI PMID

76
JordanovaA, De JongheP, BoerkoelC F, TakashimaH, De VriendtE, CeuterickC, MartinJ J, ButlerI J, ManciasP, PapasozomenosS Ch, TerespolskyD, PotockiL, BrownC W, ShyM, RitaD A, TournevI, KremenskyI, LupskiJ R, TimmermanV (2003). Mutations in the neurofilament light chain gene (NEFL) cause early onset severe Charcot-Marie-Tooth disease. Brain, 126(Pt 3): 590–597

DOI PMID

77
KeY D, SuchowerskaA K, van der HovenJ, De SilvaD M, WuC W, van EerselJ, IttnerA, IttnerL M (2012). Lessons from tau-deficient mice. Int J Alzheimers Dis, 2012: 873270

DOI PMID

78
KimC H, LismanJ E (1999). A role of actin filament in synaptic transmission and long-term potentiation. J Neurosci, 19(11): 4314–4324

PMID

79
KorobovaF, SvitkinaT (2008). Arp2/3 complex is important for filopodia formation, growth cone motility, and neuritogenesis in neuronal cells. Mol Biol Cell, 19(4): 1561–1574

DOI PMID

80
KrügerR, FischerC, SchulteT, StraussK M, MüllerT, WoitallaD, BergD, HungsM, GobbeleR, BergerK, EpplenJ T, RiessO, SchölsL (2003). Mutation analysis of the neurofilament M gene in Parkinson’s disease. Neurosci Lett, 351(2): 125–129

DOI PMID

81
KuhnT B, BamburgJ R (2008). Tropomyosin and ADF/cofilin as collaborators and competitors. Adv Exp Med Biol, 644: 232–249

DOI PMID

82
LattanteS, Le BerI, CamuzatA, BriceA, KabashiE (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

83
LavedanC, BuchholtzS, NussbaumR L, AlbinR L, PolymeropoulosM 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

DOI PMID

84
LeeM K, MarszalekJ R, ClevelandD 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

DOI PMID

85
LeeV M, GoedertM, TrojanowskiJ Q (2001). Neurodegenerative tauopathies. Annu Rev Neurosci, 24(1): 1121–1159

DOI PMID

86
LiB, ChohanM O, Grundke-IqbalI, IqbalK (2007). Disruption of microtubule network by Alzheimer abnormally hyperphosphorylated tau. Acta Neuropathol, 113(5): 501–511

DOI PMID

87
LückingC B, DürrA, BonifatiV, VaughanJ, De MicheleG, GasserT, HarhangiB S, MecoG, DenèfleP, WoodN W, AgidY, BriceA, 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

DOI PMID

88
LuoL, HenschT K, AckermanL, BarbelS, JanL Y, JanY N (1996). Differential effects of the Rac GTPase on Purkinje cell axons and dendritic trunks and spines. Nature, 379(6568): 837–840

DOI PMID

89
MaciverS K, HarringtonC R (1995). Two actin binding proteins, actin depolymerizing factor and cofilin, are associated with Hirano bodies. Neuroreport, 6(15): 1985–1988

DOI PMID

90
MahammadS, MurthyS N, DidonnaA, GrinB, IsraeliE, PerrotR, BomontP, JulienJ P, KuczmarskiE, OpalP, GoldmanR D (2013). Giant axonal neuropathy-associated gigaxonin mutations impair intermediate filament protein degradation. J Clin Invest, 123(5): 1964–1975

DOI PMID

91
ManettoV, SternbergerN H, PerryG, SternbergerL A, GambettiP (1988). Phosphorylation of neurofilaments is altered in amyotrophic lateral sclerosis. J Neuropathol Exp Neurol, 47(6): 642–653

DOI PMID

92
ManserE, LeungT, SalihuddinH, ZhaoZ S, LimL (1994). A brain serine/threonine protein kinase activated by Cdc42 and Rac1. Nature, 367(6458): 40–46

DOI PMID

93
MatusA (1988). Microtubule-associated proteins: their potential role in determining neuronal morphology. Annu Rev Neurosci, 11(1): 29–44

DOI PMID

94
MinamideL S, StrieglA M, BoyleJ A, MebergP J, BamburgJ R (2000). Neurodegenerative stimuli induce persistent ADF/cofilin-actin rods that disrupt distal neurite function. Nat Cell Biol, 2(9): 628–636

DOI PMID

95
MitchisonT J, CramerL P (1996). Actin-based cell motility and cell locomotion. Cell, 84(3): 371–379

DOI PMID

96
MockrinS C, KornE D (1980). Acanthamoeba profilin interacts with G-actin to increase the rate of exchange of actin-bound adenosine 5′-triphosphate. Biochemistry, 19(23): 5359–5362

DOI PMID

97
MorfiniG, PiginoG, MizunoN, KikkawaM, BradyS T (2007). Tau binding to microtubules does not directly affect microtubule-based vesicle motility. J Neurosci Res, 85(12): 2620–2630

DOI PMID

98
MoriwakiA, LuY F, TomizawaK, MatsuiH (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

DOI PMID

99
MorrisonB M, ShuI W, WilcoxA L, GordonJ W, MorrisonJ 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

DOI PMID

100
MunozD G, GreeneC, PerlD P, SelkoeD J (1988). Accumulation of phosphorylated neurofilaments in anterior horn motoneurons of amyotrophic lateral sclerosis patients. J Neuropathol Exp Neurol, 47(1): 9–18

DOI PMID

101
Niebroj-DoboszI, DziewulskaD, JanikP (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

102
NishidaE, IidaK, YonezawaN, KoyasuS, YaharaI, SakaiH (1987). Cofilin is a component of intranuclear and cytoplasmic actin rods induced in cultured cells. Proc Natl Acad Sci USA, 84(15): 5262–5266

DOI PMID

103
NiwaR, Nagata-OhashiK, TakeichiM, MizunoK, UemuraT (2002). Control of actin reorganization by Slingshot, a family of phosphatases that dephosphorylate ADF/cofilin. Cell, 108(2): 233–246

DOI PMID

104
OkamotoK, NagaiT, MiyawakiA, HayashiY (2004). Rapid and persistent modulation of actin dynamics regulates postsynaptic reorganization underlying bidirectional plasticity. Nat Neurosci, 7(10): 1104–1112

DOI PMID

105
OuyangY, YangX F, HuX Y, Erbayat-AltayE, ZengL H, LeeJ M, WongM (2007). Hippocampal seizures cause depolymerization of filamentous actin in neurons independent of acute morphological changes. Brain Res, 1143: 238–246

DOI PMID

106
PatrickG N, ZukerbergL, NikolicM, de la MonteS, DikkesP, TsaiL H (1999). Conversion of p35 to p25 deregulates Cdk5 activity and promotes neurodegeneration. Nature, 402(6762): 615–622

DOI PMID

107
PavlikL L, MoshkovD A (1991). Actin in synaptic cytoskeleton during long-term potentiation in hippocampal slices. Acta Histochem Suppl, 41(Supp 41): 257–264

PMID

108
Pérez-OlléR, López-ToledanoM A, GoryunovD, Cabrera-PochN, StefanisL, BrownK, LiemR K (2005). Mutations in the neurofilament light gene linked to Charcot-Marie-Tooth disease cause defects in transport. J Neurochem, 93(4): 861–874

DOI PMID

109
PerrotR, BergesR, BocquetA, EyerJ (2008). Review of the multiple aspects of neurofilament functions, and their possible contribution to neurodegeneration. Mol Neurobiol, 38(1): 27–65

DOI PMID

110
PowellK J, HoriS E, LeslieR, AndrieuxA, SchellinckH, ThorneM, RobertsonG S (2007). Cognitive impairments in the STOP null mouse model of schizophrenia. Behav Neurosci, 121(5): 826–835

DOI PMID

111
PrineasJ W, OuvrierR A, WrightR G, WalshJ C, McLeodJ G (1976). Gian axonal neuropathy—a generalized disorder of cytoplasmic microfilament formation. J Neuropathol Exp Neurol, 35(4): 458–470

DOI PMID

112
QiangL, YuW, AndreadisA, LuoM, BaasP W (2006). Tau protects microtubules in the axon from severing by katanin. J Neurosci, 26(12): 3120–3129

DOI PMID

113
RaoM V, MohanP S, KumarA, YuanA, MontagnaL, CampbellJ, Veeranna, EspreaficoE M, JulienJ P, NixonR 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

DOI PMID

114
RenY, JiangH, YangF, NakasoK, FengJ (2009). Parkin protects dopaminergic neurons against microtubule-depolymerizing toxins by attenuating microtubule-associated protein kinase activation. J Biol Chem, 284(6): 4009–4017

DOI PMID

115
RenY, ZhaoJ, FengJ (2003). Parkin binds to alpha/beta tubulin and increases their ubiquitination and degradation. J Neurosci, 23(8): 3316–3324

PMID

116
RexC S, ChenL Y, SharmaA, LiuJ, BabayanA H, GallC M, LynchG (2009). Different Rho GTPase-dependent signaling pathways initiate sequential steps in the consolidation of long-term potentiation. J Cell Biol, 186(1): 85–97

DOI PMID

117
RossiterJ P, AndersonL L, YangF, ColeG M (2000). Caspase-cleaved actin (fractin) immunolabelling of Hirano bodies. Neuropathol Appl Neurobiol, 26(4): 342–346

DOI PMID

118
RossollW, JablonkaS, AndreassiC, KröningA K, KarleK, MonaniU R, SendtnerM (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

DOI PMID

119
Rovelet-LecruxA, CampionD (2012). Copy number variations involving the microtubule-associated protein tau in human diseases. Biochem Soc Trans, 40(4): 672–676

DOI PMID

120
RoyS, ZhangB, LeeV M, TrojanowskiJ Q (2005). Axonal transport defects: a common theme in neurodegenerative diseases. Acta Neuropathol, 109(1): 5–13

DOI PMID

121
RubioM D, HaroutunianV, Meador-WoodruffJ 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

DOI PMID

122
SánchezC, ArellanoJ I, Rodríguez-SánchezP, AvilaJ, DeFelipeJ, Díez-GuerraF J (2001). Microtubule-associated protein 2 phosphorylation is decreased in the human epileptic temporal lobe cortex. Neuroscience, 107(1): 25–33

DOI PMID

123
SánchezC, Díaz-NidoJ, AvilaJ (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

DOI PMID

124
ScheibelM E, CrandallP H, ScheibelA B (1974). The hippocampal-dentate complex in temporal lobe epilepsy. A Golgi study. Epilepsia, 15(1): 55–80

DOI PMID

125
SchevzovG, CurthoysN M, GunningP W, FathT (2012). Functional diversity of actin cytoskeleton in neurons and its regulation by tropomyosin. Int Rev Cell Mol Biol, 298: 33–94

DOI PMID

126
SchmidtM L, LeeV M, TrojanowskiJ 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

PMID

127
SchneiderA B J, BiernatJ, von BergenM, MandelkowE M, MandelkowE 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

DOI PMID

128
ScottW K, NanceM A, WattsR L, HubbleJ P, KollerW C, LyonsK, PahwaR, SternM B, ColcherA, HinerB C, JankovicJ, OndoW G, AllenF H Jr, GoetzC G, SmallG W, MastermanD, MastagliaF, LaingN G, StajichJ M, SlotterbeckB, BoozeM W, RibbleR C, RampersaudE, WestS G, GibsonR A, MiddletonL T, RosesA D, HainesJ L, ScottB L, VanceJ M, Pericak-VanceM A (2001). Complete genomic screen in Parkinson disease: evidence for multiple genes. JAMA, 286(18): 2239–2244

DOI PMID

129
SeitzA, KojimaH, OiwaK, MandelkowE M, SongY H, MandelkowE (2002). Single-molecule investigation of the interference between kinesin, tau and MAP2c. EMBO J, 21(18): 4896–4905

DOI PMID

130
ShimizuH, IwayamaY, YamadaK, ToyotaT, MinabeY, NakamuraK, NakajimaM, HattoriE, MoriN, OsumiN, YoshikawaT (2006). Genetic and expression analyses of the STOP (MAP6) gene in schizophrenia. Schizophr Res, 84(2–3): 244–252

DOI PMID

131
SousaV L, BellaniS, GiannandreaM, YousufM, ValtortaF, MeldolesiJ, ChieregattiE (2009). alpha-synuclein and its A30P mutant affect actin cytoskeletal structure and dynamics. Mol Biol Cell, 20(16): 3725–3739

DOI PMID

132
SternbergerL A, SternbergerN H (1983). Monoclonal antibodies distinguish phosphorylated and nonphosphorylated forms of neurofilaments in situ. Proc Natl Acad Sci USA, 80(19): 6126–6130

DOI PMID

133
SudoH, BaasP W (2011). Strategies for diminishing katanin-based loss of microtubules in tauopathic neurodegenerative diseases. Hum Mol Genet, 20(4): 763–778

DOI PMID

134
SweetR A, HenteleffR A, ZhangW, SampsonA R, LewisD A (2009). Reduced dendritic spine density in auditory cortex of subjects with schizophrenia. Neuropsychopharmacology, 34(2): 374–389

DOI PMID

135
TakeuchiH, KobayashiY, YoshiharaT, NiwaJ, DoyuM, OhtsukaK, SobueG (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

DOI PMID

136
TilocaC, TicozziN, PensatoV, CorradoL, Del BoR, BertolinC, FenoglioC, GagliardiS, CaliniD, LauriaG, CastellottiB, BagarottiA, CortiS, GalimbertiD, CagninA, GabelliC, RanieriM, CeroniM, SicilianoG, MazziniL, CeredaC, ScarpiniE, SoraruG, ComiGP, D'AlfonsoS, GelleraC, RattiA, LandersJE, SilaniV (2013). Screening of the PFN1 gene in sporadic amyotrophic lateral sclerosis and in frontotemporal dementia. Neurobiol Aging, 34:1517 e1519–1510

137
Torres-BenitoL, RuizR, TabaresL (2012). Synaptic defects in spinal muscular atrophy animal models. Dev Neurobiol, 72(1): 126–133

DOI PMID

138
TortelliR, RuggieriM, CorteseR, D’ErricoE, CapozzoR, LeoA, MastrapasquaM, ZoccolellaS, LeanteR, LivreaP, LogroscinoG, SimoneI 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

DOI PMID

139
TrojanowskiJ Q, LeeV M Y (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

DOI PMID

140
TsengY, AnK M, EsueO, WirtzD (2004). The bimodal role of filamin in controlling the architecture and mechanics of F-actin networks. J Biol Chem, 279(3): 1819–1826

DOI PMID

141
van BlitterswijkM, BakerMC, BieniekKF, KnopmanDS, JosephsKA, BoeveB, CaselliR, WszolekZK, PetersenR, Graff-RadfordNR, BoylanKB, DicksonDW, RademakersR (2013). Profilin-1 mutations are rare in patients with amyotrophic lateral sclerosis and frontotemporal dementia. Amyotroph Lateral Scler Frontotemporal Degener14:463–469

142
WagnerU, UttonM, GalloJ M, MillerC 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

PMID

143
WongN K, HeB P, StrongM 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

PMID

144
WuC H, FalliniC, TicozziN, KeagleP J, SappP C, PiotrowskaK, LoweP, KoppersM, McKenna-YasekD, BaronD M, KostJ E, Gonzalez-PerezP, FoxA D, AdamsJ, TaroniF, TilocaC, LeclercA L, ChafeS C, MangrooD, MooreM J, ZitzewitzJ A, XuZ S, van den BergL H, GlassJ D, SicilianoG, CirulliE T, GoldsteinD B, SalachasF, MeiningerV, RossollW, RattiA, GelleraC, BoscoD A, BassellG J, SilaniV, DroryV E, BrownR H Jr, LandersJ E (2012). Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis. Nature, 488(7412): 499–503

DOI PMID

145
XieZ, SrivastavaD P, PhotowalaH, KaiL, CahillM E, WoolfreyK M, ShumC Y, SurmeierD J, PenzesP (2007). Kalirin-7 controls activity-dependent structural and functional plasticity of dendritic spines. Neuron, 56(4): 640–656

DOI PMID

146
XuZ, CorkL C, GriffinJ W, ClevelandD 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

DOI PMID

147
YangF, JiangQ, ZhaoJ, RenY, SuttonM D, FengJ (2005). Parkin stabilizes microtubules through strong binding mediated by three independent domains. J Biol Chem, 280(17): 17154–17162

DOI PMID

148
YangN, HiguchiO, OhashiK, NagataK, WadaA, KangawaK, NishidaE, MizunoK (1998). Cofilin phosphorylation by LIM-kinase 1 and its role in Rac-mediated actin reorganization. Nature, 393(6687): 809–812

DOI PMID

149
YangS, FifitaJ A, WilliamsK L, WarraichST, PamphlettR, NicholsonG A, BlairI P (2013). Mutation analysis and immunopathological studies of PFN1 in familial and sporadic amyotrophic lateral sclerosis. Neurobiol Aging, 34:2235 e2237–2210

150
YoshiharaT, YamamotoM, HattoriN, MisuK, MoriK, KoikeH, SobueG (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

DOI PMID

151
ZengL H, XuL, RensingN R, SinatraP M, RothmanS M, WongM (2007). Kainate seizures cause acute dendritic injury and actin depolymerization in vivo. J Neurosci, 27(43): 11604–11613

DOI PMID

152
ZhangB, CarrollJ, TrojanowskiJ Q, YaoY, IbaM, PotuzakJ S, HoganA M L, XieS X, BallatoreC, SmithA B 3rd, LeeV M L, BrundenK R (2012). The microtubule-stabilizing agent, epothilone D, reduces axonal dysfunction, neurotoxicity, cognitive deficits, and Alzheimer-like pathology in an interventional study with aged tau transgenic mice. J Neurosci, 32(11): 3601–3611

DOI PMID

153
ZhangB, MaitiA, ShivelyS, LakhaniF, McDonald-JonesG, BruceJ, LeeE B, XieS X, JoyceS, LiC, ToleikisP M, LeeV M, TrojanowskiJ 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

DOI PMID

154
ZhangW, BensonD L (2001). Stages of synapse development defined by dependence on F-actin. J Neurosci,21:5169–5181

155
ZhuQ, Couillard-DesprésS, JulienJ P (1997). Delayed maturation of regenerating myelinated axons in mice lacking neurofilaments. Exp Neurol, 148(1): 299–316

DOI PMID

156
ZouZY, SunQ, LiuMS, LiXG, CuiLY (2013). Mutations in the profilin 1 gene are not common in amyotrophic lateral sclerosis of Chinese origin. Neurobiol Aging, 34:1713 e1715–1716

Outlines

/