Affinage

NEFH

Neurofilament heavy polypeptide · UniProt P12036

Length
1020 aa
Mass
111.8 kDa
Annotated
2026-06-10
84 papers in source corpus 21 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NEFH encodes the largest neurofilament subunit (NF-H), an intermediate-filament protein that assembles into the heteropolymeric neurofilament network governing axonal architecture and caliber (PMID:16453600, PMID:9048736, PMID:7559762). Structurally, NF-H comprises an N-terminal alpha-helical rod domain that mediates coiled-coil co-assembly with partner subunits and an exceptionally long C-terminal tail bearing the KSP repeat motif more than 40 times (PMID:16453600, PMID:3138108). The head/rod domain is required for co-assembly, with NF-L being the preferred partner over NF-M and vimentin, and deletion into the rod produces a dominant-negative that collapses intermediate-filament networks (PMID:9048736); the C-terminal tail forms the inter-neurofilament crossbridges between parallel filaments, a function mapped to its terminal ~191 amino acids (PMID:16453600, PMID:11034913). The KSP-rich tail is massively phosphorylated in axons by neuron-specific kinases — Cdk5/p35 selectively targeting KSPXK repeats and ERK1/2 (MEK-dependent) preferring KSPXXXK motifs — and is dephosphorylated by PP2A, with phosphorylation state controlling NF-H association with microtubules (PMID:8662984, PMID:9592082, PMID:7760048, PMID:9291485). Functionally, NF-H abundance sets axonal caliber by regulating total neurofilament content: overexpression slows neurofilament transport and causes perikaryal accumulation and proximal axonal swellings, while gene disruption accelerates NF transport and raises axonal microtubule density, establishing NF-H as a regulator of the neurofilament/microtubule balance (PMID:7559762, PMID:8909545, PMID:9763430). NEFH dysfunction is linked to motor neuron disease: frameshift and stop-loss variants disrupt the network and produce aggregation-prone protein that triggers caspase-3-dependent apoptosis, and zebrafish nefh knockdown impairs motor axon development rescuable by wild-type but not mutant human NEFH (PMID:28709447, PMID:29587262).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1985 High

    Established the bipartite architecture of NF-H — defining how one subunit could both polymerize into filaments and project a phosphorylated sidearm into the inter-filament space.

    Evidence Protein-chemical fragmentation, partial sequencing, and domain isolation of NF-H

    PMID:16453600

    Open questions at the time
    • Precise residues mediating crossbridge contacts not resolved
    • Phosphorylation site sequence context not yet defined
  2. 1988 High

    Resolved the molecular basis of NF-H's massive axonal phosphorylation by identifying the >40 KSP repeats in the tail and the serine within KSP as the primary kinase target.

    Evidence Genomic cloning, exon sequencing, and structural prediction of the human NF-H gene

    PMID:3138108

    Open questions at the time
    • Identity of the responsible kinases not established at this stage
    • Functional consequence of phosphorylation not addressed
  3. 1990 High

    Showed that NF-H KSP phosphorylation depends on neuron-specific kinases absent from non-neuronal cells, explaining why robust phosphorylation is restricted to axons.

    Evidence Transfection of rat NF-H into fibroblast lines with phospho-specific immunoblotting, immunofluorescence, and EM

    PMID:2230956

    Open questions at the time
    • Specific neuronal kinases not yet identified
    • Did not test assembly partners beyond vimentin
  4. 1994 High

    Identified PP2A as the phosphatase that reverses Cdk5-type KSPXK phosphorylation, establishing the counter-regulatory arm of the phosphorylation cycle.

    Evidence In vitro dephosphorylation of pre-phosphorylated native NF-H and tail fusion protein with fractionated spinal cord phosphatases plus pharmacological inhibition

    PMID:7760048

    Open questions at the time
    • In vivo requirement for PP2A not demonstrated
    • Site-resolved dephosphorylation specificity not mapped
  5. 1994 High

    Demonstrated that head-domain phosphorylation by A-kinase modulates filament integrity differently in native heteropolymers than in NF-L homopolymers, revealing subunit-context-dependent regulation.

    Evidence In vitro kinase assay, sedimentation, and EM with stoichiometric analysis of native and reassembled neurofilaments

    PMID:8019002

    Open questions at the time
    • Physiological role of A-kinase head phosphorylation in vivo unclear
    • Relationship to tail KSP phosphorylation not addressed
  6. 1995 High

    Established NF-H abundance as a determinant of axonal caliber and showed NF-H/NF-M compete for limiting NF-L, while arguing crossbridging is not the primary driver of radial growth.

    Evidence Transgenic NF-M overexpression mice with quantitative morphometry, EM, and biochemical subunit analysis

    PMID:7559762 PMID:7790359

    Open questions at the time
    • Mechanism linking subunit ratios to transport not resolved here
    • NF packing change interpreted indirectly
  7. 1996 High

    Identified Cdk5/p35 as a physiological NF-H kinase with selectivity for KSPXK over KSPXY repeats, assigning a specific enzyme to specific tail motifs.

    Evidence Transfection with dominant-negative Cdk5, immunoprecipitation, and in vitro kinase assays on synthetic KSP peptides

    PMID:8662984

    Open questions at the time
    • Did not account for the full repertoire of KSP motif phosphorylation
    • Upstream control of p35 activation not addressed
  8. 1996 High

    Causally linked NF-H levels to neurofilament transport rate, showing overexpression slows transport and produces perikaryal accumulation and proximal swellings.

    Evidence Graded transgenic NF-H overexpression with axonal transport assays, morphometry, and EM

    PMID:8909545

    Open questions at the time
    • Molecular brake mechanism on transport not defined
    • Role of phosphorylation state in transport slowing not isolated
  9. 1997 Medium

    Connected NF-H phosphorylation to microtubule binding, showing phosphorylated NF-H co-sediments with microtubules and that aluminum exposure disrupts this phospho-dependent regulation.

    Evidence Ex vivo cosedimentation of phosphorylated vs dephosphorylated NF-H with taxol-stabilized microtubules from control and AlCl3-treated animals

    PMID:9291485

    Open questions at the time
    • Single lab with limited mechanistic follow-up
    • Direct binding interface to microtubules not mapped
    • In vivo relevance of aluminum effect uncertain
  10. 1997 High

    Dissected NF-H domain requirements for assembly, establishing the head/rod as essential for co-polymerization and NF-L as the preferred partner.

    Evidence Systematic N- and C-terminal deletion mutants co-transfected with NF-L, NF-M, and vimentin in IF-free cells

    PMID:9048736

    Open questions at the time
    • Quantitative affinities between subunits not measured
    • Tail crossbridge function not structurally resolved here
  11. 1998 High

    Genetically established NF-H as a regulator of NF transport rate and the neurofilament/microtubule balance, and as a required mediator of toxin-induced axonopathy.

    Evidence NF-H knockout mice with EM microtubule counting, radiolabel transport assays, and IDPN neurotoxin challenge

    PMID:9763430

    Open questions at the time
    • Mechanism coupling NF-H to microtubule density unknown
    • Why NF-H loss accelerates transport not molecularly defined
  12. 1998 High

    Defined ERK1/2 as a second NF-H KSP kinase with broader motif specificity than Cdk5, establishing combinatorial kinase control of the tail.

    Evidence In vitro kinase assays with recombinant kinases, synthetic KSP peptides, MEK inhibition (PD98059), and comparative kinetics versus cdk5

    PMID:9592082

    Open questions at the time
    • In vivo contribution of ERK versus Cdk5 not partitioned
    • Functional output of differential motif phosphorylation unresolved
  13. 1999 High

    Localized the crossbridging function to the C-terminal tail, particularly its terminal ~191 residues, mechanistically explaining inter-filament spacing.

    Evidence Baculovirus NF-H/NF-L co-expression in Sf9 cells with C-terminal deletion mutagenesis and EM

    PMID:11034913

    Open questions at the time
    • Role of tail phosphorylation in crossbridge formation not isolated
    • In vivo confirmation in axons not provided
  14. 1999 Medium

    Demonstrated that NF-H can dominantly interfere with assembly of another IF protein, peripherin, and that this property can be therapeutically protective by sequestering aggregation-prone subunits.

    Evidence SW13 co-assembly assays and triple-transgenic NF-L-null/peripherin/NF-H mouse crosses with axon counting

    PMID:10426285 PMID:12641746

    Open questions at the time
    • Sequestration mechanism inferred from immunohistology only
    • Single mechanistic readout in vivo
  15. 1999 Medium

    Linked Cdk5-generated NF-H phosphoepitopes to the abnormal neurofilament accumulations seen in ALS motor neurons, connecting tail phosphorylation to disease pathology.

    Evidence In vitro Cdk5 phosphorylation of recombinant side-arm fragments, epitope mapping, and ALS tissue immunohistochemistry

    PMID:10509378

    Open questions at the time
    • Single lab with limited controls
    • Causality between hyperphosphorylation and accumulation not established
  16. 1999 High

    Showed that the toxicity of excess NF-H is rescuable by restoring NF-L stoichiometry, demonstrating that neurofilament subunit balance, not NF-H per se, drives motor neuron pathology.

    Evidence Dose-dependent transgenic hNF-L co-expression and adenoviral hNF-L delivery in NF-H-overexpressing mice with transport and morphometric readouts

    PMID:10515233

    Open questions at the time
    • Molecular basis of stoichiometric rescue not defined
    • Applicability to human disease not tested
  17. 2017 Medium

    Provided a gain-of-function disease mechanism: frameshift mutations recruit a cryptic amyloidogenic element from the 3'UTR, producing aggregation-prone NEFH that triggers apoptotic motor neuron death.

    Evidence Patient mutation analysis, neuroblastoma aggregation and caspase-3 assays, and in vivo chick embryo spinal cord electroporation

    PMID:28709447

    Open questions at the time
    • Single lab
    • Frequency and penetrance in patient populations not established
    • Aggregate clearance pathway only partially characterized
  18. 2018 Medium

    Extended the loss/gain-of-function disease model with a stop-loss variant disrupting the network and aggregating in cells, and demonstrated an in vivo requirement for nefh in motor axon development.

    Evidence SW13 co-assembly assays with mutant/WT NEFH and zebrafish morpholino knockdown with WT versus mutant mRNA rescue

    PMID:29587262

    Open questions at the time
    • Single lab
    • Morpholino off-target effects not fully excluded
    • Mechanism of network disruption by extra C-terminal residues not resolved
  19. 2018 Medium

    Implicated post-transcriptional miRNA control as a route to disrupted NEFH stoichiometry in ALS, broadening disease mechanisms beyond coding mutations.

    Evidence miRNA target validation in neuronal cells and qPCR/Western correlation in ALS spinal cord homogenates

    PMID:30029677

    Open questions at the time
    • Correlational tissue data with limited mechanistic resolution
    • Causal link between miRNA dysregulation and motor neuron loss not demonstrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How NF-H tail phosphorylation state is mechanistically coupled to the neurofilament transport brake and to microtubule density regulation in vivo remains unresolved.
  • No structural model of the phosphorylated tail in the crossbridge or microtubule-bound state
  • Relative in vivo contributions of Cdk5, ERK1/2, and PP2A to axonal NF-H phosphostate not partitioned
  • Causal chain from subunit stoichiometry imbalance to motor neuron death incompletely defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0008092 cytoskeletal protein binding 1
Localization
GO:0005856 cytoskeleton 3
Partners
CDK5MAPK1NEFLNEFMPRPHVIM
Complex memberships
neurofilament

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1985 NF-H protein contains an N-terminal alpha-helical rod domain (intermediate filament-type) that enables coiled-coil interactions with other neurofilament subunits, and a uniquely long C-terminal tail domain (the 'sidearm') rich in proline, lysine, and glutamic acid that carries serine phosphates restricted to the amino-terminal part of the tail, which is responsible for inter-neurofilament crossbridges in axons. Protein biochemistry (chymotryptic fragmentation, partial amino acid sequencing, biochemical characterization of isolated domain fractions) The EMBO journal High 16453600
1988 The human NF-H gene encodes a central alpha-helical rod domain (approximately 310 aa) capable of coiled-coil interactions, and an exceptionally long C-terminal tail (>600 aa) containing the KSP (Lys-Ser-Pro) repeat motif more than 40 times; the serine within KSP is the primary target for NF-directed kinases in vivo, explaining massive axonal phosphorylation of NF-H. Genomic cloning, exon sequencing, intron/exon mapping, predicted protein structure analysis The EMBO journal High 3138108
1990 When transfected into vimentin-containing fibroblasts (L tk-, L929, 3T6), NF-H co-assembles with vimentin to form copolymers, but remains predominantly non-phosphorylated on KSP sequences, indicating that the NF-H-specific KSP kinases are absent from fibroblasts and are neuron-specific. Transfection of rat NF-H cDNA into fibroblast cell lines, immunofluorescence, electron microscopy, 1D and 2D gel electrophoresis with phospho-specific antibodies The Journal of neuroscience High 2230956
1994 Protein phosphatase 2A (PP2A) is the primary phosphatase that dephosphorylates cdk5-phosphorylated KSPXK repeat motifs in NF-H, as demonstrated by in vitro dephosphorylation of 32P-labeled NF-H and NF-H tail fusion protein using partially purified phosphatase fractions from rat spinal cord. In vitro phosphatase assay with cdk5-pre-phosphorylated NF-H substrates (native NF preparation and bacterially expressed C-terminal tail), column chromatography fractionation, Western blot, pharmacological inhibition Journal of neurochemistry High 7760048
1994 Phosphorylation of NF-H head domain by cAMP-dependent protein kinase (A-kinase) in native neurofilaments (NF-L/NF-M/NF-H trimers) causes partial filament fragmentation/thinning rather than complete disassembly, in contrast to purified NF-L homopolymers which fully disassemble; A-kinase phosphorylates NF-H at approximately 4 mol/mol in native NF. In vitro kinase assay, sedimentation experiments, electron microscopy, stoichiometric phosphorylation analysis of native and reassembled neurofilaments Molecular biology of the cell High 8019002
1995 NF-H abundance is a primary determinant of axonal caliber: transgenic mice with increased NF-M showed proportionate decreases in axonal NF-H and reduced axonal cross-sectional area, indicating NF-H and NF-M compete for co-assembly with limiting NF-L or as substrates for axonal transport; nearest-neighbor spacing between neurofilaments was unaffected, arguing against a primary crossbridging role in radial growth. Transgenic mouse overexpression of NF-M, quantitative morphometry, immunohistochemistry, electron microscopy, biochemical analysis of NF subunit levels and phosphorylation The Journal of cell biology High 7559762
1995 Overexpression of NFM in transgenic mice reduces levels of the most heavily phosphorylated NFH isoforms in brain and increases neurofilament packing density in large CNS axons, suggesting reduced NFH phosphorylation is a compensatory response that allows denser NF packing. Transgenic mouse overexpression, Western blotting, electron microscopy of CNS axons, quantitative subunit analysis The Journal of cell biology Medium 7790359
1996 Cdk5 in conjunction with its activator p35 phosphorylates NF-H in vivo; Cdk5 selectively phosphorylates KSPXK repeats rather than KSPXY repeats in the NF-H tail domain, as shown by transfection assays with dominant-negative Cdk5 mutant and immunoprecipitation. cDNA cloning of rat Cdk5 and p35, transient transfection into cells, dominant-negative Cdk5 mutagenesis, immunoprecipitation, in vitro kinase assay with synthetic KSP peptides The Journal of biological chemistry High 8662984
1996 Increasing NF-H expression selectively slows neurofilament transport into and along axons, resulting in perikaryal accumulation of neurofilaments and proximal axonal swellings; NF-H abundance modulates axonal caliber by regulating total neurofilament content. Transgenic mouse overexpression of wild-type mouse NF-H at up to 4.5-fold normal levels, axonal transport assays, morphometry, immunohistochemistry, electron microscopy The Journal of cell biology High 8909545
1997 NF-H head domain (N-terminal) is required for co-assembly with NF-L and vimentin; the C-terminal tail is not required for co-assembly with vimentin but is important for forming extensive filamentous NF-L/NF-H networks; deletion into the alpha-helical rod creates a dominant-negative mutant that disrupts all intermediate filament networks; NF-L is the preferred assembly partner of NF-H over vimentin and NF-M. Transient co-transfection of amino- and carboxy-terminal deletion mutants of NF-H with NF-L, NF-M, and vimentin into cell lines lacking cytoplasmic IFs, immunofluorescence microscopy Journal of neurochemistry High 9048736
1998 Disruption of the NF-H gene in mice causes approximately 2.4-fold increase in axonal microtubule density and increased velocity of neurofilament transport of NF-L and NF-M in motor axons, indicating NF-H is a key regulator of neurofilament transport rate and modulates the balance between neurofilament and microtubule content in axons. Targeted gene disruption (NF-H knockout mouse), electron microscopy (microtubule counting), [35S]methionine axonal transport assay, biochemical fractionation (tubulin/NF-L ratios in sciatic nerve) The Journal of cell biology High 9763430
1998 ERK1 and ERK2 (MAPK) phosphorylate all types of KSP motifs in NF-H and NF-M (KSPXK, KSPXXK, KSPXXXK, KSPXXXXK), with preferred substrate being KSPXXXK peptide; cdk5 by contrast only phosphorylates KSPXK. ERK1/2 phosphorylation of NF-H is MEK-dependent and can be inhibited by PD98059. Column chromatography fractionation of rat brain, Western blot, kinase identification by protein sequencing, in vitro kinase assay with synthetic KSP peptides and expressed NF-H polypeptides, dephosphorylated native NF-H, MEK inhibitor PD98059, comparative kinetics of Erk2 vs cdk5 The Journal of neuroscience High 9592082
1998 NF-H subunit is a key mediator of IDPN (beta,beta'-iminodipropionitrile)-induced axonopathy: NF-H knockout mice were protected from IDPN-induced neurofilamentous swellings that normally occur in wild-type motor neurons. NF-H knockout mice treated with IDPN neurotoxin, histological analysis of motor neuron swellings, comparison with heterozygous and homozygous knockout littermates The Journal of cell biology High 9763430
1999 Co-expression of NF-H and NF-L in Sf9 cells using baculovirus produces 10 nm filaments with frequent crossbridges between parallel filaments; deletion analysis shows the C-terminal tail domain of NF-H forms the crossbridges and promotes parallel bundle formation; the last 191 amino acids of the C-terminal tail play a key role in crossbridge formation. Baculovirus co-expression of NF-H and NF-L in Sf9 cells, C-terminal deletion mutagenesis, electron microscopy Journal of cell science High 11034913
1999 Co-expression of NF-H with peripherin in SW13 cells (devoid of cytoplasmic IFs) disrupts peripherin assembly, while NF-L and peripherin co-assemble normally, demonstrating that NF-H interferes with peripherin filament formation through direct interaction. SW13 cell transfection with individual and pairwise combinations of neurofilament subunits and peripherin, immunofluorescence microscopy Biochemistry and cell biology Medium 10426285
1999 Overexpression of hNF-L rescues motor neuron disease caused by excess hNF-H in transgenic mice in a dosage-dependent manner, reducing perikaryal swellings, relieving axonal transport defects, and restoring axonal radial growth; adenoviral delivery of hNF-L in adult mice also reduced perikaryal swellings. Transgenic mouse co-expression of hNF-H and hNF-L, axon counting, transport analysis, morphometry; adenoviral gene delivery in adult mice Journal of neuropathology and experimental neurology High 10515233
2003 NF-H overexpression rescues peripherin-mediated motor neuron degeneration in NF-L null mice by sequestering peripherin into the perikaryon, preventing formation of axonal IF inclusions that block axonal transport. Transgenic mouse cross (NF-L null x peripherin overexpressor x NF-H overexpressor), axon counting in L5 ventral roots, histological analysis of inclusion localization Journal of neurochemistry Medium 12641746
1997 Phosphorylated NF-H preferentially co-sediments with polymerized microtubules; dephosphorylation abolishes this interaction under normal conditions. Following in vivo aluminum exposure, dephosphorylated NF-H from treated animals retains its microtubule-binding capacity (4.5-fold induction), indicating that in vivo AlCl3 disrupts the normal phosphorylation-dependent regulation of NF-H/microtubule cross-linking. Ex vivo cosedimentation assay of purified NF-H with taxol-stabilized microtubules, comparison of phosphorylated vs. alkaline phosphatase-treated NF-H from control and AlCl3-treated rabbits, silver-staining densitometry Neurotoxicology Medium 9291485
2017 Frameshift mutations near the end of the NEFH coding sequence introduce a cryptic amyloidogenic element (CAE) encoded by the 3'UTR, causing protein aggregation in motoneurons recognized by the autophagic pathway and triggering caspase-3-dependent apoptosis; in vivo electroporation of chick embryo spinal cord confirmed mutant NEFH forms aggregates and triggers apoptosis. Patient mutation identification, expression of mutant NEFH in neuroblastoma cells (aggregation assay, caspase-3 activation), in vivo chick embryo electroporation Acta neuropathologica communications Medium 28709447
2018 A small set of ALS-linked miRNAs that are upregulated in ALS spinal cord directly regulate NEFH mRNA levels in human spinal motor neurons; dysregulation of these miRNAs is associated with increased NFH protein levels in ALS spinal cord homogenates, suggesting altered miRNA-mediated post-transcriptional control of NEFH contributes to disrupted neurofilament stoichiometry in ALS. miRNA target prediction and validation in neuronal cell lines, quantitative PCR and Western blot of ALS spinal cord homogenates, correlation analysis Molecular brain Medium 30029677
2018 A NEFH frameshift variant (c.3057insG) causes stop-loss and translation of 41 additional amino acids; mutant NEFH disrupts the neurofilament network and induces NEFH protein aggregation in SW13 (vim-) cells; knockdown of nefh in zebrafish impairs motor axon development and motor ability, phenotypes rescued by wild-type but not mutant human NEFH mRNA. Co-transfection of mutant/wild-type NEFH with NF-L in SW13 cells (immunofluorescence), morpholino nefh knockdown in zebrafish, mRNA rescue experiments Neuro-degenerative diseases Medium 29587262
1999 Cdk5 phosphorylates NF-H heavy chain side-arms to generate epitopes recognized by antibodies that label neurofilament accumulations in ALS motor neurons; mapping using recombinant NF-H side-arm fragments defined the epitope locations for several antibodies. In vitro kinase assay (Cdk5 phosphorylation of recombinant NF-H fragments), recombinant fragment epitope mapping, immunohistochemistry of ALS motor neurons Progress in neuro-psychopharmacology & biological psychiatry Medium 10509378

Source papers

Stage 0 corpus · 84 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1988 The structure and organization of the human heavy neurofilament subunit (NF-H) and the gene encoding it. The EMBO journal 240 3138108
1998 Mitogen-activated protein kinases (Erk1,2) phosphorylate Lys-Ser-Pro (KSP) repeats in neurofilament proteins NF-H and NF-M. The Journal of neuroscience : the official journal of the Society for Neuroscience 171 9592082
2005 Hyperphosphorylated neurofilament NF-H is a serum biomarker of axonal injury. Biochemical and biophysical research communications 166 16176808
1996 Neurofilament subunit NF-H modulates axonal diameter by selectively slowing neurofilament transport. The Journal of cell biology 150 8909545
1995 Increasing neurofilament subunit NF-M expression reduces axonal NF-H, inhibits radial growth, and results in neurofilamentous accumulation in motor neurons. The Journal of cell biology 131 7559762
1996 Phosphorylation of the high molecular weight neurofilament protein (NF-H) by Cdk5 and p35. The Journal of biological chemistry 126 8662984
1985 Protein-chemical characterization of NF-H, the largest mammalian neurofilament component; intermediate filament-type sequences followed by a unique carboxy-terminal extension. The EMBO journal 116 16453600
2008 The phosphorylated axonal form of the neurofilament subunit NF-H (pNF-H) as a blood biomarker of traumatic brain injury. Journal of neurotrauma 114 18729720
1998 Disruption of the NF-H gene increases axonal microtubule content and velocity of neurofilament transport: relief of axonopathy resulting from the toxin beta,beta'-iminodipropionitrile. The Journal of cell biology 113 9763430
2014 Toxicity of TDCPP and TCEP on PC12 cell: changes in CAMKII, GAP43, tubulin and NF-H gene and protein levels. Toxicology letters 108 24717766
1990 Transfected rat high-molecular-weight neurofilament (NF-H) coassembles with vimentin in a predominantly nonphosphorylated form. The Journal of neuroscience : the official journal of the Society for Neuroscience 104 2230956
2012 The usefulness of S100B, NSE, GFAP, NF-H, secretagogin and Hsp70 as a predictive biomarker of outcome in children with traumatic brain injury. Acta neurochirurgica 103 21976236
1995 Overexpression of the human NFM subunit in transgenic mice modifies the level of endogenous NFL and the phosphorylation state of NFH subunits. The Journal of cell biology 82 7790359
1999 Interactions between peripherin and neurofilaments in cultured cells: disruption of peripherin assembly by the NF-M and NF-H subunits. Biochemistry and cell biology = Biochimie et biologie cellulaire 74 10426285
1995 Neuronal cyclin-dependent kinase-5 phosphorylation sites in neurofilament protein (NF-H) are dephosphorylated by protein phosphatase 2A. Journal of neurochemistry 71 7760048
2008 Detection of phosphorylated NF-H in the cerebrospinal fluid and blood of aneurysmal subarachnoid hemorrhage patients. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 67 18319731
1989 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. Proceedings of the National Academy of Sciences of the United States of America 67 2928342
2004 Decreased expression of NEFH and PCP4/PEP19 in the prefrontal cortex of alcoholics. Neuroscience research 66 15236863
1999 Extra neurofilament NF-L subunits rescue motor neuron disease caused by overexpression of the human NF-H gene in mice. Journal of neuropathology and experimental neurology 64 10515233
2000 Overexpression of neurofilament subunit NF-L and NF-H extends survival of a mouse model for amyotrophic lateral sclerosis. Neuroscience letters 62 10686419
1994 Phosphorylation of native and reassembled neurofilaments composed of NF-L, NF-M, and NF-H by the catalytic subunit of cAMP-dependent protein kinase. Molecular biology of the cell 60 8019002
2000 The C-terminal tail domain of neurofilament protein-H (NF-H) forms the crossbridges and regulates neurofilament bundle formation. Journal of cell science 55 11034913
1999 Cyclin dependent kinase-5 (CDK-5) phosphorylates neurofilament heavy (NF-H) chain to generate epitopes for antibodies that label neurofilament accumulations in amyotrophic lateral sclerosis (ALS) and is present in affected motor neurones in ALS. Progress in neuro-psychopharmacology & biological psychiatry 48 10509378
2011 Hyperphosphorylated neurofilament NF-H as a predictor of mortality after brain injury in children. Brain injury 46 21219092
2016 A Four-Gene Promoter Methylation Marker Panel Consisting of GREM1, NEURL, LAD1, and NEFH Predicts Survival of Clear Cell Renal Cell Cancer Patients. Clinical cancer research : an official journal of the American Association for Cancer Research 45 27756787
1988 The large neurofilament subunit (NF-H) of the rat: cDNA cloning and in situ detection. Biochemical and biophysical research communications 42 2457365
1986 Isolation of a cDNA for the rat heavy neurofilament polypeptide (NF-H). FEBS letters 42 2878828
1999 Increased vulnerability of NFH-LacZ transgenic mouse to traumatic brain injury-induced behavioral deficits and cortical damage. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 41 10413031
2000 The neuronal Golgi apparatus is fragmented in transgenic mice expressing a mutant human SOD1, but not in mice expressing the human NF-H gene. Journal of the neurological sciences 40 10675581
2003 Peripherin-mediated death of motor neurons rescued by overexpression of neurofilament NF-H proteins. Journal of neurochemistry 38 12641746
1994 Changes in neurofilament protein NF-L and NF-H immunoreactivity following kainic acid-induced seizures. Journal of neurochemistry 36 8294936
2018 Dysregulation of human NEFM and NEFH mRNA stability by ALS-linked miRNAs. Molecular brain 34 30029677
1988 The structure of the largest murine neurofilament protein (NF-H) as revealed by cDNA and genomic sequences. Brain research 32 3145094
2001 Neurofilament proteins NF-L, NF-M and NF-H in brain of patients with Down syndrome and Alzheimer's disease. Amino acids 29 11764410
2017 Cryptic amyloidogenic elements in mutant NEFH causing Charcot-Marie-Tooth 2 trigger aggresome formation and neuronal death. Acta neuropathologica communications 25 28709447
1988 The gene encoding the large human neurofilament subunit (NF-H) maps to the q121-q131 region on human chromosome 22. Human genetics 25 3192217
2016 Altered CSNK1E, FABP4 and NEFH protein levels in the dorsolateral prefrontal cortex in schizophrenia. Schizophrenia research 24 27236410
1994 Antibodies to different isoforms of the heavy neurofilament protein (NF-H) in normal aging and Alzheimer's disease. Molecular neurobiology 24 7888108
1988 Partial sequence of the rat heavy neurofilament polypeptide (NF-H). Identification of putative phosphorylation sites. FEBS letters 24 3143606
1994 Dose-dependent selective suppression of light (NFL) and medium (NFM) but not heavy (NFH) molecular weight neurofilament mRNA levels in acute aluminum neurotoxicity. Molecular and cellular neurosciences 22 7804601
1997 Assembly properties of amino- and carboxyl-terminally truncated neurofilament NF-H proteins with NF-L and NF-M in the presence and absence of vimentin. Journal of neurochemistry 20 9048736
1997 Expression of p67 (Munc-18), Cdk5, P-NFH and syntaxin during development of the rat cerebellum. Developmental neuroscience 20 9097032
1991 Expression of the neurofilament protein NF-H in L cells. Journal of neuroscience research 19 1795408
1996 Spinal motor neuron neuroaxonal spheroids in chronic aluminum neurotoxicity contain phosphatase-resistant high molecular weight neurofilament (NFH). Toxicology 16 8644113
1992 Diminished concentration of the NF-H subunit of neurofilaments in cerebral cortex of rats chronically treated with proline, methylmalonate and phenylalanine plus alpha-methylphenylalanine. Journal of inherited metabolic disease 16 1527992
2024 Unveiling the NEFH+ malignant cell subtype: Insights from single-cell RNA sequencing in prostate cancer progression and tumor microenvironment interactions. Frontiers in immunology 15 39759507
2000 Neurofilament-rich intraneuronal inclusions exacerbate neurodegenerative sequelae of brain trauma in NFH/LacZ transgenic mice. Experimental neurology 14 10964487
1991 In situ localization of NF-H neurofilament subunit mRNAs in rat brain. Developmental neuroscience 14 2070748
2021 Charcot-Marie-Tooth disease type 2CC due to NEFH variants causes a progressive, non-length-dependent, motor-predominant phenotype. Journal of neurology, neurosurgery, and psychiatry 13 34518334
2017 Axonal Charcot-Marie-Tooth neuropathy concurrent with distal and proximal weakness by translational elongation of the 3' UTR in NEFH. Journal of the peripheral nervous system : JPNS 13 28544463
2014 Phosphorylated neurofilament subunit NF-H becomes elevated in the cerebrospinal fluid of patients with acutely worsening symptoms of compression myelopathy. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 13 25065845
1993 Expression of phosphorylated high molecular weight neurofilament protein (NF-H) and vimentin in human developing dorsal root ganglia and spinal cord. Histochemistry 13 8163392
2020 Novel 199 base pair NEFH promoter drives expression in retinal ganglion cells. Scientific reports 12 33020509
2005 Allelic variants of the canine heavy neurofilament (NFH) subunit and extensive phosphorylation in dogs with motor neuron disease. Journal of comparative pathology 12 15629478
2003 Characterization of NFH-LacZ transgenic mice with the SHIRPA primary screening battery and tests of motor coordination, exploratory activity, and spatial learning. Behavioural processes 12 12763264
1988 cDNA coding for the tail region of the high molecular weight rabbit neurofilament protein NF-H. Journal of neuroscience research 12 3138432
2018 Whole-Genome Linkage Analysis with Whole-Exome Sequencing Identifies a Novel Frameshift Variant in NEFH in a Chinese Family with Charcot-Marie-Tooth 2: A Novel Variant in NEFH for Charcot-Marie-Tooth 2. Neuro-degenerative diseases 11 29587262
1991 Monoclonal antibodies to the heavy neurofilament subunit (NF-H) of Torpedo cholinergic neurons. Journal of neuroscience research 11 1791640
1995 Expression of subtypes NF-L, NF-M and NF-H of neurofilament triplet proteins in the developing rat inner ear. ORL; journal for oto-rhino-laryngology and its related specialties 10 7478449
1989 HincII RFLP in the human gene for the heavy neurofilament subunit (NF-H). Nucleic acids research 10 2570412
2021 Proximal weakness involvement in the first Italian case of Charcot-Marie-Tooth 2CC harboring a novel frameshift variant in NEFH. Journal of the peripheral nervous system : JPNS 9 33987933
2018 Overexpression of MAP2 and NF-H Associated with Dendritic Pathology in the Spinal Cord of Mice Infected with Rabies Virus. Viruses 9 29509660
2024 PiRNA-4447944 promotes castration-resistant growth and metastasis of prostate cancer by inhibiting NEFH expression through forming the piRNA-4447944-PIWIL2-NEFH complex. International journal of biological sciences 8 38993562
2023 CHRDL1, NEFH, TAGLN and SYNM as novel diagnostic biomarkers of benign prostatic hyperplasia and prostate cancer. Cancer biomarkers : section A of Disease markers 8 37781794
2021 Sequencing of neurofilament genes identified NEFH Ser787Arg as a novel risk variant of sporadic amyotrophic lateral sclerosis in Chinese subjects. BMC medical genomics 8 34511133
2020 A novel missense pathogenic variant in NEFH causing rare Charcot-Marie-Tooth neuropathy type 2CC. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 8 32780247
1991 A possible mechanism of action of the neurotoxic agent iminodipropionitrile (IDPN): a selective aggregation of the medium and heavy neurofilament polypeptides (NF-M and NF-H). Brain research 8 1884214
1990 Cyclic AMP-dependent expression of the heavy neurofilament (NF-H) polypeptide in differentiating neuroblastoma cells. Brain research. Molecular brain research 8 2160043
2012 Axonal regeneration is compromised in NFH-LacZ transgenic mice but not in NFH-GFP mice. Neuroscience 7 23079625
2009 Hypophosphorylation of NF-H and NF-M subunits of neurofilaments and the associated decrease in KSPXK kinase activity in the sciatic nerves of swiss white mice inoculated in the foot pad with mycobacterium leprae. Leprosy review 6 20306637
2003 Selective changes in the neurofilament and microtubule cytoskeleton of NF-H/LacZ mice. Journal of neuroscience research 6 12503082
2001 Delayed expression of the NFH subunit in differentiating P19 cells. Brain research. Developmental brain research 6 11744113
2022 An NEFH founder mutation causes broad phenotypic spectrum in multiple Japanese families. Journal of human genetics 5 35091664
2022 Expression of the NSE,SP,NFH and DβH in normal and cryptorchid testes of Bactrian camel. Animal reproduction 5 35154438
2002 NFH-LacZ transgenic mice: regional brain activity of cytochrome oxidase. Experimental neurology 5 12429197
2024 Comparison of SNCG and NEFH Promoter-Driven Expression of Human SIRT1 Expression in a Mouse Model of Glaucoma. Translational vision science & technology 4 39177995
1997 Enhanced ex vivo cosedimentation of high molecular weight neurofilament protein (NFH) with microtubules following in vivo aluminum chloride exposure: inhibition of dephosphorylation-dependent dissociation. Neurotoxicology 4 9291485
1995 Phosphorylation and dephosphorylation of distinct isoforms of the heavy neurofilament protein NF-H. Cellular and molecular neurobiology 4 8590456
2018 Complete Genome Sequence of Lactobacillus curvatus NFH-Km12, Isolated from the Japanese Traditional Fish Fermented Food Kabura-zushi. Microbiology resource announcements 3 30533612
2025 Association of Reduced Brain Metabolism With Motor Function and Survival in Amyotrophic Lateral Sclerosis Patients With Neurofilament Heavy (NEFH) Gene Mutation. European journal of neurology 2 40607881
2006 Tpc1808 increases expression of NF-H in PC12 cells. Journal of molecular neuroscience : MN 2 16954602
2025 Genetic targeting of myelinated primary afferent neurons using a new NefhCreERT2 knock-in mouse. Scientific reports 1 40158013
2022 A novel single-point mutation of NEFH and biallelic SACS mutation presenting as intermediate form Charcot-Marie-Tooth: A case report in Vietnam. Surgical neurology international 1 36600740
2025 Correction: Unveiling the NEFH+ malignant cell subtype: insights from single-cell RNA sequencing in prostate cancer progression and tumor microenvironment interactions. Frontiers in immunology 0 41280907

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