Gene Symbol: Nefh
Description: neurofilament heavy
Alias: Nfh, neurofilament heavy polypeptide, 200 kDa neurofilament protein, NF-H, neurofilament triplet H protein, neurofilament, heavy polypeptide
Species: rat
Products:     Nefh

Top Publications

  1. Jacomy H, Zhu Q, Couillard Despres S, Beaulieu J, Julien J. Disruption of type IV intermediate filament network in mice lacking the neurofilament medium and heavy subunits. J Neurochem. 1999;73:972-84 pubmed
    ..The combined results demonstrate a requirement of the high-molecular-weight subunits for the assembly of type IV intermediate filament proteins and for the efficient translocation of NF-L proteins into the axonal compartment. ..
  2. Lees J, Shneidman P, Skuntz S, Carden M, Lazzarini R. The structure and organization of the human heavy neurofilament subunit (NF-H) and the gene encoding it. EMBO J. 1988;7:1947-55 pubmed
    ..The human NF-H gene has three introns, two of which interrupt the protein-coding sequence at identical points to introns in the genes for the two smaller NF proteins, NF-M and NF-L.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  3. Eyer J, Peterson A. Neurofilament-deficient axons and perikaryal aggregates in viable transgenic mice expressing a neurofilament-beta-galactosidase fusion protein. Neuron. 1994;12:389-405 pubmed
    ..mice expressing a fusion protein in which the carboxyl terminus of the high molecular weight neurofilament protein (NFH) was replaced by beta-galactosidase. The transgene, regulated by NFH sequences, was expressed in projection neurons...
  4. Collard J, Cote F, Julien J. Defective axonal transport in a transgenic mouse model of amyotrophic lateral sclerosis. Nature. 1995;375:61-4 pubmed
  5. Lieberburg I, Spinner N, Snyder S, Anderson J, Goldgaber D, Smulowitz M, et al. Cloning of a cDNA encoding the rat high molecular weight neurofilament peptide (NF-H): developmental and tissue expression in the rat, and mapping of its human homologue to chromosomes 1 and 22. Proc Natl Acad Sci U S A. 1989;86:2463-7 pubmed
    ..In situ hybridizations performed on human chromosomes mapped the NF-H gene to chromosomes 1 and 22. Whether one copy is a pseudogene remains to be determined. ..
  6. Pant A, Veeranna -, Pant H, Amin N. Phosphorylation of human high molecular weight neurofilament protein (hNF-H) by neuronal cyclin-dependent kinase 5 (cdk5). Brain Res. 1997;765:259-66 pubmed
    ..It is proposed that neuronal cdk5 regulates phosphorylation of the KSPXK motif in hNF-H and other cytoskeletal proteins with similar motifs in the nervous system. ..
  7. Chen J, Nakata T, Zhang Z, Hirokawa N. The C-terminal tail domain of neurofilament protein-H (NF-H) forms the crossbridges and regulates neurofilament bundle formation. J Cell Sci. 2000;113 Pt 21:3861-9 pubmed
    ..The last 191 amino acids of the C-terminal tail domain of NF-H play a key role in crossbridge formation. ..
  8. Schenker M, Riederer B, Kuntzer T, Barakat Walter I. Thyroid hormones stimulate expression and modification of cytoskeletal protein during rat sciatic nerve regeneration. Brain Res. 2002;957:259-70 pubmed
    ..These results help us to understand partially the mechanism by which thyroid hormones enhance peripheral nerve regeneration. The stimulating effect of T3 on peripheral nerve regeneration may have considerable therapeutic potential. ..
  9. Klosen P, van den Bosch de Aguilar P. Spontaneous perikaryal neurofilament phosphorylation in the septofimbrial nucleus of the rat. Neurosci Lett. 1992;139:108-13 pubmed
    ..Our observations, as well as previous studies by other authors, indicate that perikaryal neurofilament phosphorylation is not necessarily linked to pathological conditions. ..

More Information


  1. Kaczmarski W, Barua M, Mazur Kolecka B, Frackowiak J, Dowjat W, Mehta P, et al. Intracellular distribution of differentially phosphorylated dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A). J Neurosci Res. 2014;92:162-73 pubmed publisher
    ..This study supports the hypothesis that intracellular distribution and compartment-specific functions of DYRK1A may depend on its phosphorylation pattern. ..
  2. Athlan E, Mushynski W. Heterodimeric associations between neuronal intermediate filament proteins. J Biol Chem. 1997;272:31073-8 pubmed
    Formation of protein dimers involving alpha-internexin, peripherin, and the neurofilament (NF) proteins NFH, NFM, and NFL was investigated by partial renaturation of various combinations of individually purified subunits in buffered 2 M ..
  3. Reynolds R, Burri R, Herschkowitz N. Retarded development of neurons and oligodendroglia in rat forebrain produced by hyperphenylalaninemia results in permanent deficits in myelin despite long recovery periods. Exp Neurol. 1993;124:357-67 pubmed
  4. Shen Z, Lu H, Li X, Xu D, Hu J, Wang X. [Tetramethylpyrazine accelerated spinal cord repair through regulation of caspase-3 and neurofilament protein expression: an acute spinal cord injury model in rats]. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2008;33:693-9 pubmed
    ..Tetramethylpyrazine improves spinal cord healing through regulation of caspase-3 and neurofilament protein expression. ..
  5. DeCaprio A, Kinney E, Fowke J. Regioselective binding of 2,5-hexanedione to high-molecular-weight rat neurofilament proteins in vitro. Toxicol Appl Pharmacol. 1997;145:211-7 pubmed
    ..These results provide additional support for limited and specific binding of 2,5-HD to neurofilaments and indicate that the phosphorylation state of the protein may not substantially influence this binding. ..
  6. Robinson P, Wion D, Anderton B. Isolation of a cDNA for the rat heavy neurofilament polypeptide (NF-H). FEBS Lett. 1986;209:203-5 pubmed
    ..A repeat peptide sequence that may be a multiphosphorylation site was identified in the C-terminal non-helical tail. ..
  7. Yang J, Seo J, Nair R, Han S, Jang S, Kim K, et al. DGK? regulates presynaptic release during mGluR-dependent LTD. EMBO J. 2011;30:165-80 pubmed publisher
    ..These results suggest that DGK? requires PSD-95 family proteins for synaptic localization and regulates presynaptic DAG signalling and neurotransmitter release during mGluR-LTD. ..
  8. Rudrabhatla P, Jaffe H, Pant H. Direct evidence of phosphorylated neuronal intermediate filament proteins in neurofibrillary tangles (NFTs): phosphoproteomics of Alzheimer's NFTs. FASEB J. 2011;25:3896-905 pubmed publisher
    ..In corresponding matched control preparations of PHF/NFTs, none of these phosphorylated neuronal cytoskeletal proteins were found. These studies independently demonstrate that NF proteins are an integral part of NFTs in AD brains. ..
  9. Vahidnia A, Romijn F, van der Voet G, de Wolff F. Arsenic-induced neurotoxicity in relation to toxicokinetics: effects on sciatic nerve proteins. Chem Biol Interact. 2008;176:188-95 pubmed publisher
    ..In addition, hyperphosphorylation of NF-L and MAP-tau by As also contribute to destabilization and disruption of the cytoskeletal framework, which eventually may lead to axonal degeneration. ..
  10. Lopez Picon F, Uusi Oukari M, Holopainen I. Differential expression and localization of the phosphorylated and nonphosphorylated neurofilaments during the early postnatal development of rat hippocampus. Hippocampus. 2003;13:767-79 pubmed
    ..These developmental changes could be of importance in determining the reactivity of hippocampal neurons in pathological conditions in the immature hippocampus. ..
  11. Dautigny A, Pham Dinh D, Roussel C, Felix J, Nussbaum J, Jolles P. The large neurofilament subunit (NF-H) of the rat: cDNA cloning and in situ detection. Biochem Biophys Res Commun. 1988;154:1099-106 pubmed
    ..Specific localization in neurons of the corresponding mRNA was demonstrated by in situ hybridization using the pNF-H1 as a probe. ..
  12. Geddes J, Bondada V, Tekirian T, Pang Z, Siman R. Perikaryal accumulation and proteolysis of neurofilament proteins in the post-mortem rat brain. Neurobiol Aging. 1995;16:651-60 pubmed
    ..These results demonstrate that the levels and localization of neurofilament proteins observed in tissues obtained at autopsy even with short postmortem intervals may not accurately reflect the premortem condition. ..
  13. Elder G, Friedrich V, Kang C, Bosco P, Gourov A, Tu P, et al. Requirement of heavy neurofilament subunit in the development of axons with large calibers. J Cell Biol. 1998;143:195-205 pubmed
    ..These results demonstrate directly that unlike losing the NF-L or NF-M subunits, loss of NF-H has only a slight effect on NF number in axons. Yet NF-H plays a major role in the development of large diameter axons. ..
  14. Yamamoto W, Sugiura A, Nakazato Imasato E, Kita Y. Characterization of primary sensory neurons mediating static and dynamic allodynia in rat chronic constriction injury model. J Pharm Pharmacol. 2008;60:717-22 pubmed publisher
  15. Wen H, Lin Y, Ting C, Lin Chao S, Li H, Hsieh Li H. Stathmin, a microtubule-destabilizing protein, is dysregulated in spinal muscular atrophy. Hum Mol Genet. 2010;19:1766-78 pubmed publisher
    ..We conclude that aberrant stathmin levels may play a detrimental role in SMA; this finding suggests a novel approach to treating SMA by enhancing microtubule stability. ..
  16. Ghosh S, Rahaman S, Sarkar P. Regulation of neurofilament gene expression by thyroid hormone in the developing rat brain. Neuroreport. 1999;10:2361-5 pubmed
    ..The overall results show that TH plays an important role in regulating the expression of all three NF genes during rat brain development. ..
  17. Yu S, Son F, Yu J, Zhao X, Yu L, Li G, et al. Acrylamide alters cytoskeletal protein level in rat sciatic nerves. Neurochem Res. 2006;31:1197-204 pubmed
    ..These findings suggest that ACR altered the cytoskeletal protein level in sciatic nerve, which may be one of the molecular mechanisms of ACR-induced peripheral neuropathy. ..
  18. Shen H, Barry D, Garcia M. Distal to proximal development of peripheral nerves requires the expression of neurofilament heavy. Neuroscience. 2010;170:16-21 pubmed publisher
  19. Schlaepfer W, Bruce J. Simultaneous up-regulation of neurofilament proteins during the postnatal development of the rat nervous system. J Neurosci Res. 1990;25:39-49 pubmed
  20. Takahashi N, Ishizuka B. The involvement of neurofilament heavy chain phosphorylation in the maturation and degeneration of rat oocytes. Endocrinology. 2012;153:1990-8 pubmed publisher
  21. Faussone Pellegrini M, Matini P, DeFelici M. The cytoskeleton of the myenteric neurons during murine embryonic life. Anat Embryol (Berl). 1999;199:459-69 pubmed
  22. Tsuda M, Tashiro T, Komiya Y. Selective solubilization of high-molecular-mass neurofilament subunit during nerve regeneration. J Neurochem. 2000;74:860-8 pubmed
    ..The low-molecular-mass subunit remained in the insoluble fraction in both the normal and the regenerating nerves, indicating that selective solubilization of NF-H rather than total filament disassembly occurs during regeneration. ..
  23. al Chalabi A, Andersen P, Nilsson P, Chioza B, Andersson J, Russ C, et al. Deletions of the heavy neurofilament subunit tail in amyotrophic lateral sclerosis. Hum Mol Genet. 1999;8:157-64 pubmed
    ..The heavy neurofilament subunit (NFH) tail is composed of a repeating amino acid motif, usually X-lysine-serine-proline-Y-lysine (XKSPYK), where X is a ..
  24. Fornaro M, Lee J, Raimondo S, Nicolino S, Geuna S, Giacobini Robecchi M. Neuronal intermediate filament expression in rat dorsal root ganglia sensory neurons: an in vivo and in vitro study. Neuroscience. 2008;153:1153-63 pubmed publisher
  25. Stubbs E, Lawlor M, Richards M, Siddiqui K, Fisher M, Bhoopalam N, et al. Anti-neurofilament antibodies in neuropathy with monoclonal gammopathy of undetermined significance produce experimental motor nerve conduction block. Acta Neuropathol. 2003;105:109-16 pubmed
    ..IgG MGUS neuropathy patients that react strongly on immunoblot with a high molecular weight neurofilament protein (NFH)...
  26. Sasaki T, Ishiguro K, Hisanaga S. Novel axonal distribution of neurofilament-H phosphorylated at the glycogen synthase kinase 3beta-phosphorylation site in its E-segment. J Neurosci Res. 2009;87:3088-97 pubmed publisher
    ..These results indicate that Ser493 in the NF-H E-segment is a novel site that is phosphorylated in both the myelinated and the unmyelinated regions of axons. ..
  27. Liang W, Zhang W, Zhao S, Li Q, Liang H, Ceng R. Altered expression of neurofilament 200 and amyloid-β peptide (1-40) in a rat model of chronic cerebral hypoperfusion. Neurol Sci. 2015;36:707-12 pubmed publisher
    ..Our data demonstrate that CCH leads to axonal damage over time. We also confirmed that the expression of Aβ (1-40) and NF200 may be useful biomarkers of axonal damage following CCH. ..
  28. Ueno T, Ohori Y, Ito J, Hoshikawa S, Yamamoto S, Nakamura K, et al. Hyperphosphorylated neurofilament NF-H as a biomarker of the efficacy of minocycline therapy for spinal cord injury. Spinal Cord. 2011;49:333-6 pubmed publisher
    ..Rats with lower plasma pNF-H levels at 3 dpi had higher hind limb motor score at 28 dpi. pNF-H levels may serve as a biomarker for evaluating the efficacy of therapies for SCI. ..
  29. Anderson K, Scheff S, Miller K, Roberts K, Gilmer L, Yang C, et al. The phosphorylated axonal form of the neurofilament subunit NF-H (pNF-H) as a blood biomarker of traumatic brain injury. J Neurotrauma. 2008;25:1079-85 pubmed publisher
    ..These findings suggest that the measurement of blood levels of pNF-H is a convenient method for assessing neuropathology following TBI. ..
  30. Yuan A, Rao M, Kumar A, Julien J, Nixon R. Neurofilament transport in vivo minimally requires hetero-oligomer formation. J Neurosci. 2003;23:9452-8 pubmed
    ..They also show that NF-M can partner with intermediate filament proteins other than the NF-H and NF-L subunits in neurons to support slow transport and possibly other functions of neuronal intermediate filaments. ..
  31. Garcia M, Lobsiger C, Shah S, Deerinck T, Crum J, Young D, et al. NF-M is an essential target for the myelin-directed "outside-in" signaling cascade that mediates radial axonal growth. J Cell Biol. 2003;163:1011-20 pubmed
    ..This has revealed that the tail domain of NF-M, with seven KSP motifs, is an essential target for the myelination-dependent outside-in signaling cascade that determines axonal caliber and conduction velocity of motor axons. ..
  32. Goldstein M, Weiss S, Lazzarini R, Shneidman P, Lees J, Schlaepfer W. mRNA levels of all three neurofilament proteins decline following nerve transection. Brain Res. 1988;427:287-91 pubmed
    ..The early and co-terminal fall in mRNAs suggests that the 3 NF genes are regulated by common factor(s) and that the function of these factor(s) is influenced by the state of axonal continuity with the target organ. ..
  33. Camargo de Morais M, De Freitas M, De Mattos A, Schroder N, Zilles A, Lisboa C, et al. Effects of brain ischemia on intermediate filaments of rat hippocampus. Neurochem Res. 1996;21:595-602 pubmed
    ..These results suggest that transient ischemia followed by reperfusion causes proteolysis of intermediate filaments in the hippocampus, and the proteolysis could be facilitated by diminished phosphorylation levels of NF-M and NF-L. ..
  34. Breen K, Robinson P, Wion D, Anderton B. Partial sequence of the rat heavy neurofilament polypeptide (NF-H). Identification of putative phosphorylation sites. FEBS Lett. 1988;241:213-8 pubmed
    ..There is, however, one region which is variable between the species, this being the highly phosphorylated region of the protein containing the Lys-Ser-Pro triplet repeat. ..
  35. Chiasson K, Lahaie Collins V, Bournival J, Delapierre B, Gélinas S, Martinoli M. Oxidative stress and 17-alpha- and 17-beta-estradiol modulate neurofilaments differently. J Mol Neurosci. 2006;30:297-310 pubmed
    ..We measured gene expression and protein expression of each NF subunit, NFL, NFM, and NFH, by semiquantitative RT-PCR, Western blot, and immunofluorescence...
  36. Duchala C, Shick H, Garcia J, Deweese D, Sun X, Stewart V, et al. The toppler mouse: a novel mutant exhibiting loss of Purkinje cells. J Comp Neurol. 2004;476:113-29 pubmed
    ..Given the changes in both Purkinje cells and glia in toppler cerebellum, this may be a very useful model in which to investigate the developmental interaction of Purkinje cells and Bergmann glia. ..
  37. Zamoner A, Heimfarth L, Pessoa Pureur R. Congenital hypothyroidism is associated with intermediate filament misregulation, glutamate transporters down-regulation and MAPK activation in developing rat brain. Neurotoxicology. 2008;29:1092-9 pubmed publisher
    ..These events could be somehow related to the neurological dysfunction described in hypothyroidism. ..
  38. Sayers N, Beswick L, Middlemas A, Calcutt N, Mizisin A, Tomlinson D, et al. Neurotrophin-3 prevents the proximal accumulation of neurofilament proteins in sensory neurons of streptozocin-induced diabetic rats. Diabetes. 2003;52:2372-80 pubmed
    ..It is proposed that the accumulation of NF-H and NF-M subunits in the proximal axon is an etiologic factor in the distal axon degeneration observed in diabetes. ..
  39. Park M, Jang J, Song J, Lee H, Oh S. Neurofilament heavy chain expression and neuroplasticity in rat auditory cortex after unilateral and bilateral deafness. Hear Res. 2016;339:155-60 pubmed publisher
    ..Neurofilament heavy chain (NEFH) mRNA expression and SMI-32-ir protein levels were increased in the BD group...
  40. Kesavapany S, Patel V, Zheng Y, Pareek T, Bjelogrlic M, Albers W, et al. Inhibition of Pin1 reduces glutamate-induced perikaryal accumulation of phosphorylated neurofilament-H in neurons. Mol Biol Cell. 2007;18:3645-55 pubmed
  41. Chin S, Liem R. Transfected rat high-molecular-weight neurofilament (NF-H) coassembles with vimentin in a predominantly nonphosphorylated form. J Neurosci. 1990;10:3714-26 pubmed
    ..The stable NF-H-expressing cell lines can therefore be used to study these putative neurofilament kinases in vitro and in vivo. ..
  42. Liu Z, Gao W, Wang Y, Zhang W, Liu H, Li Z. Neuregulin-1? regulates outgrowth of neurites and migration of neurofilament 200 neurons from dorsal root ganglial explants in vitro. Peptides. 2011;32:1244-8 pubmed publisher
    ..The data in this study imply that NRG-1? promotes neurite outgrowth and neuronal migration from DRG explants in vitro. ..
  43. Zhang W, Li H, Xing Z, Yuan H, Kindy M, Li Z. Expression of mRNAs for PPT, CGRP, NF-200, and MAP-2 in cocultures of dissociated DRG neurons and skeletal muscle cells in administration of NGF or NT-3. Folia Histochem Cytobiol. 2012;50:312-8 pubmed
  44. Sasaki T, Taoka M, Ishiguro K, Uchida A, Saito T, Isobe T, et al. In vivo and in vitro phosphorylation at Ser-493 in the glutamate (E)-segment of neurofilament-H subunit by glycogen synthase kinase 3beta. J Biol Chem. 2002;277:36032-9 pubmed
    ..GSK3beta in the spinal cord extract was associated with NF cytoskeletons. Taken together, we concluded that Ser-493 in the E-segment of NF-H is phosphorylated by GSK3beta in rat spinal cords. ..
  45. Narayana P, HERRERA J, Bockhorst K, Esparza Coss E, Xia Y, Steinberg J, et al. Chronic cocaine administration causes extensive white matter damage in brain: diffusion tensor imaging and immunohistochemistry studies. Psychiatry Res. 2014;221:220-30 pubmed publisher
    ..Increased GAP-43 suggests drug-induced plasticity or a possible repair mechanism response. The findings indicated that multiple white matter tracts are affected following chronic cocaine exposure. ..
  46. Rebelo A, Abrams A, Cottenie E, Horga A, Gonzalez M, Bis D, et al. Cryptic Amyloidogenic Elements in the 3' UTRs of Neurofilament Genes Trigger Axonal Neuropathy. Am J Hum Genet. 2016;98:597-614 pubmed publisher
    ..These families carry distinct frameshift variants in NEFH (neurofilament heavy), leading to a loss of the terminating codon and translation of the 3' UTR into an extra 40 ..
  47. Pennypacker K, Fischer I, Levitt P. Early in vitro genesis and differentiation of axons and dendrites by hippocampal neurons analyzed quantitatively with neurofilament-H and microtubule-associated protein 2 antibodies. Exp Neurol. 1991;111:25-35 pubmed
    ..Our data also indicate that NF-H is detectable early in primary neurite development and that, based on in vivo localization and morphology of cultured neurites, the phosphorylated form of NF-H is concentrated in axons. ..
  48. Rudrabhatla P, Zheng Y, Amin N, Kesavapany S, Albers W, Pant H. Pin1-dependent prolyl isomerization modulates the stress-induced phosphorylation of high molecular weight neurofilament protein. J Biol Chem. 2008;283:26737-47 pubmed publisher
    ..Thus, Pin1 may be a potential therapeutic target for these diseases. ..