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Gene Review

Nefh  -  neurofilament, heavy polypeptide

Rattus norvegicus

Synonyms: 200 kDa neurofilament protein, NF-H, Neurofilament heavy polypeptide, Neurofilament triplet H protein, Nfh
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Disease relevance of Nefh


Psychiatry related information on Nefh

  • Postnatal developmental profiles of filamentous actin and of 200 kDa neurofilament polypeptide in the visual cortex of light- and dark-reared rats and their relationship to critical period plasticity [6].
  • Previous studies from our laboratory suggest that Alzheimer's disease sera contain a repertoire of antibodies to the heavy neurofilament subunit (NF-H) and that a subpopulation of these antibodies bind specifically to epitopes highly enriched in NF-H isolated from the purely cholinergic electromotor neurons of Torpedo [7].
  • The results indicate that morphine addiction is associated with an aberrant hyperphophorylation of NF-H in the rat brain [8].
  • Production of such Abs in EAD rats by prolonged immunization with Torpedo cholinergic NF-H results in the accumulation of IgG in the septum and hippocampus of the immunized rats and in memory deficits [9].

High impact information on Nefh


Biological context of Nefh


Anatomical context of Nefh


Associations of Nefh with chemical compounds

  • This suggests that glutamate causes increased NF-H phosphorylation at least in part by activation of stress activated protein kinases [23].
  • Phosphorylation of NF-H by the cdc2-like activity was not affected by 3 microM olomoucine but was inhibited by 10 microM of this kinase inhibitor [24].
  • In the control nerve, 15-25% of high-molecular-mass NF subunit (NF-H) was recovered in the 1% Triton-soluble fraction when fractionated in the presence of phosphatase inhibitors [25].
  • In this study, neurofilament (NF) proteins were examined following intraperitoneal injection of kainic acid, and special reference was given to temporal changes in quantity and quality of the NF light (NF-L) and heavy (NF-H) subunits [22].
  • No alterations of the light subunit of neurofilament proteins occurred, suggesting that KA has a preferential effect on NF-H phosphorylation [26].

Enzymatic interactions of Nefh

  • We conclude that cdk-5 and GSK-3 phosphorylate different residues or sets of residues within NF-H sidearm in cells [27].

Regulatory relationships of Nefh


Other interactions of Nefh


Analytical, diagnostic and therapeutic context of Nefh


  1. Distribution of a novel 57 kDa intermediate filament (IF) protein in the nervous system. Parysek, L.M., Goldman, R.D. J. Neurosci. (1988) [Pubmed]
  2. Neurofilaments are transported rapidly but intermittently in axons: implications for slow axonal transport. Roy, S., Coffee, P., Smith, G., Liem, R.K., Brady, S.T., Black, M.M. J. Neurosci. (2000) [Pubmed]
  3. Alterations of a 200 kDa neurofilament in the rat hippocampus after forebrain ischemia. Kaku, Y., Yonekawa, Y., Tsukahara, T., Ogata, N., Kimura, T., Taniguchi, T. J. Cereb. Blood Flow Metab. (1993) [Pubmed]
  4. Protection from MPTP-induced neurotoxicity in differentiating mouse N2a neuroblastoma cells. De Girolamo, L.A., Hargreaves, A.J., Billett, E.E. J. Neurochem. (2001) [Pubmed]
  5. Neurofilament proteins are constitutively expressed in F9 teratocarcinoma cells. Murtomäki, S., Virtanen, I., Liesi, P. Int. J. Dev. Neurosci. (1999) [Pubmed]
  6. Postnatal developmental profiles of filamentous actin and of 200 kDa neurofilament polypeptide in the visual cortex of light- and dark-reared rats and their relationship to critical period plasticity. Nona, S.N., Trowell, S.C., Cronly-Dillon, J.R. FEBS Lett. (1985) [Pubmed]
  7. Monoclonal antibodies to the heavy neurofilament subunit (NF-H) of Torpedo cholinergic neurons. Faigon, M., Hadas, E., Alroy, G., Chapman, J., Auerbach, J.M., Michaelson, D.M. J. Neurosci. Res. (1991) [Pubmed]
  8. Acute and chronic effects of morphine and naloxone on the phosphorylation of neurofilament-H proteins in the rat brain. Jaquet, P.E., Ferrer-Alcón, M., Ventayol, P., Guimón, J., García-Sevilla, J.A. Neurosci. Lett. (2001) [Pubmed]
  9. Decreased density of forebrain cholinergic neurons and disintegration of the spatial organization of behavior in experimental autoimmune dementia (EAD). Michaelson, D.M., Dubovik, V., Faigon, M., Eilam, D., Feldon, J. Ann. N. Y. Acad. Sci. (1993) [Pubmed]
  10. Mitogen-activated protein kinases (Erk1,2) phosphorylate Lys-Ser-Pro (KSP) repeats in neurofilament proteins NF-H and NF-M. Veeranna, n.u.l.l., Amin, N.D., Ahn, N.G., Jaffe, H., Winters, C.A., Grant, P., Pant, H.C. J. Neurosci. (1998) [Pubmed]
  11. Transfected rat high-molecular-weight neurofilament (NF-H) coassembles with vimentin in a predominantly nonphosphorylated form. Chin, S.S., Liem, R.K. J. Neurosci. (1990) [Pubmed]
  12. Characterization of intermediate filaments in PC12 cells. Parysek, L.M., Goldman, R.D. J. Neurosci. (1987) [Pubmed]
  13. Neurotrophin-3 prevents the proximal accumulation of neurofilament proteins in sensory neurons of streptozocin-induced diabetic rats. Sayers, N.M., Beswick, L.J., Middlemas, A., Calcutt, N.A., Mizisin, A.P., Tomlinson, D.R., Fernyhough, P. Diabetes (2003) [Pubmed]
  14. Isolation of a cDNA for the rat heavy neurofilament polypeptide (NF-H). Robinson, P.A., Wion, D., Anderton, B.H. FEBS Lett. (1986) [Pubmed]
  15. Augmented locomotor recovery after spinal cord injury in the athymic nude rat. Potas, J.R., Zheng, Y., Moussa, C., Venn, M., Gorrie, C.A., Deng, C., Waite, P.M. J. Neurotrauma (2006) [Pubmed]
  16. Phosphorylation of the high molecular weight neurofilament protein (NF-H) by Cdk5 and p35. Sun, D., Leung, C.L., Liem, R.K. J. Biol. Chem. (1996) [Pubmed]
  17. Morphological and biochemical changes of neurofilaments in aged rat sciatic nerve axons. Uchida, A., Tashiro, T., Komiya, Y., Yorifuji, H., Kishimoto, T., Hisanaga, S. J. Neurochem. (2004) [Pubmed]
  18. Soma neurofilament immunoreactivity is related to cell size and fibre conduction velocity in rat primary sensory neurons. Lawson, S.N., Waddell, P.J. J. Physiol. (Lond.) (1991) [Pubmed]
  19. The calpain inhibitor MDL-28170 and the AMPA/KA receptor antagonist CNQX inhibit neurofilament degradation and enhance neuronal survival in kainic acid-treated hippocampal slice cultures. Lopez-Picon, F.R., Kukko-Lukjanov, T.K., Holopainen, I.E. Eur. J. Neurosci. (2006) [Pubmed]
  20. Monoclonal antibodies distinguish several differentially phosphorylated states of the two largest rat neurofilament subunits (NF-H and NF-M) and demonstrate their existence in the normal nervous system of adult rats. Lee, V.M., Carden, M.J., Schlaepfer, W.W., Trojanowski, J.Q. J. Neurosci. (1987) [Pubmed]
  21. On the role of the 200-kDa neurofilament protein at the developing neuromuscular junction. Donahue, S.P., Wood, J.G., English, A.W. Dev. Biol. (1988) [Pubmed]
  22. Changes in neurofilament protein NF-L and NF-H immunoreactivity following kainic acid-induced seizures. Wang, S., Hamberger, A., Yang, Q., Haglid, K.G. J. Neurochem. (1994) [Pubmed]
  23. Phosphorylation of neurofilament heavy chain side-arms by stress activated protein kinase-1b/Jun N-terminal kinase-3. Brownlees, J., Yates, A., Bajaj, N.P., Davis, D., Anderton, B.H., Leigh, P.N., Shaw, C.E., Miller, C.C. J. Cell. Sci. (2000) [Pubmed]
  24. A cdc2-like kinase distinct from cdk5 is associated with neurofilaments. Starr, R., Hall, F.L., Monteiro, M.J. J. Cell. Sci. (1996) [Pubmed]
  25. Selective solubilization of high-molecular-mass neurofilament subunit during nerve regeneration. Tsuda, M., Tashiro, T., Komiya, Y. J. Neurochem. (2000) [Pubmed]
  26. In vivo activation of kainate receptors induces dephosphorylation of the heavy neurofilament subunit. Wang, S., Hamberger, A., Ding, M., Haglid, K.G. J. Neurochem. (1992) [Pubmed]
  27. Differential cellular phosphorylation of neurofilament heavy side-arms by glycogen synthase kinase-3 and cyclin-dependent kinase-5. Guidato, S., Tsai, L.H., Woodgett, J., Miller, C.C. J. Neurochem. (1996) [Pubmed]
  28. Rat olfactory neurons express a 200 kDa neurofilament. Bruch, R.C., Carr, V.M. Brain Res. (1991) [Pubmed]
  29. Vanilloid receptor homologue, VRL1, is expressed by both A- and C-fiber sensory neurons. Ma, Q.P. Neuroreport (2001) [Pubmed]
  30. Phosphorylation of rat brain cytoskeletal proteins is increased after orally administered aluminum. Johnson, G.V., Jope, R.S. Brain Res. (1988) [Pubmed]
  31. The hippocampus in spontaneously hypertensive rats: an animal model of vascular dementia? Sabbatini, M., Catalani, A., Consoli, C., Marletta, N., Tomassoni, D., Avola, R. Mech. Ageing Dev. (2002) [Pubmed]
  32. Slow transport rates of cytoskeletal proteins change during regeneration of axotomized retinal neurons in adult rats. McKerracher, L., Vidal-Sanz, M., Aguayo, A.J. J. Neurosci. (1990) [Pubmed]
  33. Quantitative and qualitative alterations of neuronal and glial intermediate filaments in rat nervous system after exposure to 2,5-hexanedione. Karlsson, J.E., Rosengren, L.E., Haglid, K.G. J. Neurochem. (1991) [Pubmed]
  34. Cellular reactivity to mechanical axonal injury in an organotypic in vitro model of neurotrauma. Sieg, F., Wahle, P., Pape, H.C. J. Neurotrauma (1999) [Pubmed]
  35. Neurofilament mRNAs are present and translated in the normal and severed sciatic nerve. Sotelo-Silveira, J.R., Calliari, A., Kun, A., Benech, J.C., Sanguinetti, C., Chalar, C., Sotelo, J.R. J. Neurosci. Res. (2000) [Pubmed]
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