Affinage

NEFL

Neurofilament light polypeptide · UniProt P07196

Length
543 aa
Mass
61.5 kDa
Annotated
2026-04-29
100 papers in source corpus 23 papers cited in narrative 23 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NEFL encodes neurofilament light chain, the obligate backbone subunit of neuronal 10-nm intermediate filaments that is essential for axonal caliber, neurofilament-dependent axonal transport, and sensorimotor function. NF-L self-assembles and co-assembles with NF-M into heteropolymer filaments, a process negatively regulated by head-domain phosphorylation at Ser-26/Ser-57 by Rho-kinase and by cAMP-dependent kinase, and positively modulated by small heat shock proteins HspB1 and HspB5 that slow polymerization kinetics (PMID:9571164, PMID:8670258, PMID:28000086, PMID:19147253). NEFL mRNA stability is post-transcriptionally controlled by 14-3-3 protein binding to 3′ UTR hexanucleotide motifs and by specific microRNAs including miR-381 and miR-25 (PMID:17098443, PMID:25605243, PMID:26209061). Recessive nonsense mutations cause NMD-mediated mRNA depletion and complete absence of neurofilaments, while dominant missense mutations in distinct domains produce filament misassembly and aggregation, both mechanisms underlying Charcot–Marie–Tooth neuropathy (PMID:29888333, PMID:20039262, PMID:23618875).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1985 High

    Determining the complete primary structure of NF-L revealed it as a divergent intermediate filament family member, establishing the sequence framework for all subsequent structure–function studies.

    Evidence Complete amino acid sequencing of porcine NF-L by protein chemistry

    PMID:3920075

    Open questions at the time
    • Three-dimensional structure not determined
    • Post-translational modification sites not yet mapped
  2. 1989 High

    Reconstitution of NF-L filament assembly in non-neuronal cells demonstrated that NF-L is intrinsically competent to form 10-nm filaments and can copolymerize with vimentin, resolving whether neuron-specific cofactors were required.

    Evidence Transfection of NF-L into L cells; immunofluorescence and solubility fractionation

    PMID:2493000

    Open questions at the time
    • Stoichiometry of NF-L/vimentin copolymers undefined
    • Regulation of assembly not addressed
  3. 1995 High

    Functional dissection of the NF-L promoter identified cAMP- and NGF-responsive elements, establishing the transcriptional control architecture driving neuron-specific NF-L expression.

    Evidence Promoter-CAT reporter assays, DNase I footprinting, and gel-shift in PC12 cells

    PMID:7745611

    Open questions at the time
    • In vivo chromatin context not examined
    • Upstream signaling cascades linking NGF receptor to these elements not fully mapped
  4. 1996 High

    Demonstrating that cAMP-dependent phosphorylation blocks a late stage of NF-L/NF-M coassembly established head-domain phosphorylation as a key negative regulator of neurofilament polymerization.

    Evidence In vitro phosphorylation with sedimentation and electron microscopy of reconstituted filaments

    PMID:8670258

    Open questions at the time
    • Identity of the specific kinase(s) acting in vivo not determined
    • Phosphorylation site(s) not mapped in this study
  5. 1998 High

    Identification of Rho-kinase phosphorylation at Ser-26 and Ser-57 as sufficient for filament disassembly provided the first site-specific mechanism linking a signaling pathway to neurofilament dynamics.

    Evidence In vitro kinase assay with MALDI-TOF site identification and EM of disassembled filaments

    PMID:9571164

    Open questions at the time
    • In vivo relevance of Rho-kinase phosphorylation at these sites not confirmed
    • Whether dephosphorylation reverses disassembly not tested
  6. 2005 Medium

    NFL knockout mice revealed that loss of NF-L is sufficient to cause sensorimotor dysfunction and spatial learning deficits, establishing NF-L as required for normal neuronal function beyond structural support.

    Evidence Behavioral battery and cytochrome oxidase histochemistry in Nefl−/− mice

    PMID:15884021

    Open questions at the time
    • Mechanism linking NF-L loss to metabolic and cognitive changes unclear
    • Single laboratory study
  7. 2006 High

    Discovery that 14-3-3 proteins bind NEFL mRNA 3′ UTR hexanucleotide motifs and regulate mRNA stability revealed a post-transcriptional layer of NF-L regulation independent of transcription or phosphorylation.

    Evidence LC/MS/MS identification of 14-3-3 on NEFL 3′ UTR; mutagenesis of binding motifs with mRNA stability readout

    PMID:17098443

    Open questions at the time
    • Physiological conditions triggering 14-3-3 binding changes unknown
    • Downstream decay machinery not identified
  8. 2009 High

    Phosphomimetic mutations at head-domain sites blocked axonal transport in living neurons, directly linking NF-L phosphorylation state to neurofilament motility and not just assembly.

    Evidence Site-directed mutagenesis with live-cell axonal transport imaging in cultured neurons

    PMID:19147253

    Open questions at the time
    • Motor protein(s) affected by phosphorylation state not identified
    • Contribution of individual sites not resolved
  9. 2009 High

    The finding that a homozygous NEFL nonsense mutation (E210X) abolishes filament network formation without dominant-negative effects, combined with absent neurofilaments and reduced axonal caliber in patient nerve, established a loss-of-function basis for recessive CMT neuropathy.

    Evidence SW13 vim(−) cell assembly assay and sural nerve biopsy ultrastructure from an affected patient

    PMID:20039262

    Open questions at the time
    • Whether other recessive mutations share identical mechanism not tested
    • Degree of NF-M/NF-H compensation unclear
  10. 2009 Medium

    NFL−/− mice showed aberrant cytosolic TDP-43 accumulation and caspase-3-dependent neuronal death after axotomy, revealing NF-L as a determinant of TDP-43 localization and neuronal survival after injury.

    Evidence Axotomy in Nefl−/− mice with immunohistochemistry for TDP-43, PGRN, and caspase-3

    PMID:19619516

    Open questions at the time
    • Direct physical interaction between NF-L and TDP-43 not demonstrated
    • Mechanism connecting NF-L absence to TDP-43 mislocalization unknown
    • Single laboratory study
  11. 2013 Medium

    Demonstration that domain-specific NEFL mutations (Q333P vs P8R) are differentially rescued by distinct chaperones (HSPA1 vs HSPB1) established that CMT-linked mutations cause structurally distinct misfolding defects.

    Evidence SW13 cell assembly assay, in vitro refolding, chaperone induction, and live motor neuron imaging

    PMID:23618875

    Open questions at the time
    • Structural basis of differential chaperone sensitivity not resolved
    • In vivo therapeutic potential of chaperone induction not tested
  12. 2016 High

    Quantitative biophysical analysis of HspB1 and HspB5 binding to NFL at defined stoichiometry (~1:2 HspB1:NFL) and kinetic slowing of polymerization established small heat shock proteins as direct modulators of neurofilament assembly dynamics.

    Evidence Differential centrifugation, analytical ultracentrifugation, and fluorescence polymerization kinetics with recombinant proteins

    PMID:28000086

    Open questions at the time
    • In vivo stoichiometry and regulation of sHsp–NFL interaction unknown
    • Effect on mixed NF-L/NF-M/NF-H filaments not tested
  13. 2018 High

    Patient iPSC-derived motor neurons confirmed that recessive NEFL nonsense mutations cause near-complete mRNA loss via NMD, with pharmacological NMD inhibition partially rescuing NEFL mRNA, definitively establishing the molecular mechanism of recessive NEFL-CMT.

    Evidence iPSC motor neurons; qPCR, Western blot, EM, single-cell transcriptomics, NMD inhibitor rescue

    PMID:29888333

    Open questions at the time
    • Whether NMD inhibition can restore sufficient protein for functional rescue in vivo unknown
    • Long-term consequences of partial NEFL restoration not assessed

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis of NF-L assembly and the identity of motor proteins whose interaction with neurofilaments is regulated by head-domain phosphorylation remain unresolved, as does the mechanism by which NF-L loss leads to TDP-43 mislocalization.
  • No high-resolution structure of assembled NF-L filament
  • Motor adaptor linking phosphorylation to transport not identified
  • Direct NF-L–TDP-43 interaction not tested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3
Localization
GO:0005856 cytoskeleton 3
Pathway
R-HSA-112316 Neuronal System 4 R-HSA-1266738 Developmental Biology 3
Partners
CRYABHSPB1MTMR2NEFMVIMYWHAB
Complex memberships
neurofilament (NF-L/NF-M/NF-H)

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 NF-L and NF-M polypeptides, when expressed in non-neuronal fibroblasts (L cells), are competent to assemble into intermediate filament arrays in the absence of neuron-specific factors, and NF-L-containing filaments form copolymers with vimentin as judged by immunofluorescence and altered vimentin solubility. Transient and stable DNA transfection into L cells; immunofluorescence; solubility fractionation The Journal of cell biology High 2493000
1985 Porcine NF-L (NEFL) is a 548-residue protein (~62 kDa actual mass, ~68-72 kDa by gel electrophoresis) and sequence comparison reveals NF proteins are the most divergent members among non-epithelial intermediate filament proteins, with NF-L, NF-M, and NF-H sharing lower sequence identity with each other than do GFAP, desmin, and vimentin. Complete amino acid sequencing by protein chemistry; sequence comparison FEBS letters High 3920075
1998 Rho-associated kinase (Rho-kinase) phosphorylates bovine NF-L in vitro at Ser-26 and Ser-57 in the head domain (~1 mol phosphate/mol NF-L), and this phosphorylation causes disassembly of 10-nm NF-L filaments. In vitro kinase assay; MALDI/TOF peptide mapping; electron microscopy of filaments Biochemical and biophysical research communications High 9571164
1996 cAMP-dependent phosphorylation of NF-L or NF-M inhibits their coassembly into heteropolymer filaments in vitro, blocking a late stage of filament assembly while still permitting formation of heterooligomeric assembly intermediates. In vitro phosphorylation; sedimentation velocity; electron microscopy of reconstituted filaments Biochemical and biophysical research communications High 8670258
2009 Phosphorylation of the NFL head domain regulates axonal transport of neurofilaments: mutation of three or four phosphorylation sites to mimic permanent phosphorylation inhibits axonal transport and disrupts neurofilament assembly, while mutation to preclude phosphorylation has no effect on transport. Site-directed mutagenesis of NFL phosphorylation sites; live-cell axonal transport monitoring in neurons European journal of cell biology High 19147253
2009 A homozygous nonsense mutation in NEFL (E210X) causes loss of function: the truncated protein fails to form an intermediate filament network and does not dominantly interfere with wild-type NF-L filament formation in SW-13 vim(-) cells; nerve biopsy shows absence of intermediate filaments in remaining axons, confirming neurofilaments as the main determinant of axonal caliber. Cell culture filament assembly assay in SW-13 vim(-) cells; sural nerve biopsy immunohistochemistry and electron microscopy Annals of neurology High 20039262
1991 NF-L immunoreactivity defines a distinct subpopulation of large sensory neurons in rat dorsal root ganglia (DRG) that is peripherin-negative; a small population (~6%) co-expresses both NF-L and peripherin; this pattern is maintained in neonatal DRG cultures, establishing NF-L as a marker of large myelinated sensory neurons. Double immunofluorescence with anti-NF-L and anti-peripherin antibodies on DRG sections and cultures Journal of neuroscience research Medium 1795410
1995 The rat NF-L gene promoter contains a cAMP-responsive element between -97 and -38 bp and an NGF-responsive element between -38 and +75 bp; NGF treatment induces up to 12-fold stimulation of NF-L promoter-driven expression in PC12 cells via transient binding of transcription factors to Sp1, AP-2, and CGCCCCCGC elements. Promoter-CAT reporter transfection assays; DNase I hypersensitivity mapping; gel-shift assays Journal of neuroscience research High 7745611
2006 14-3-3 proteins (beta, zeta, tau, gamma, eta isoforms) bind directly to the NEFL mRNA 3′ UTR at two hexanucleotide motifs identified by LC/MS/MS, and mutation of these motifs reduces 14-3-3 interaction and alters mRNA stability, establishing 14-3-3 as a regulator of NFL mRNA stability. LC/MS/MS peptide identification; in vitro RNA-binding assay; site-directed mutagenesis of UTR motifs; mRNA stability measurement Molecular and cellular neurosciences High 17098443
2010 Human RGNEF (homologue of mouse p190RhoGEF) directly interacts with human NFL mRNA in vitro by gel shift assay; in ALS tissue lysates this interaction is detected by IP-RT-PCR, but not in control lysates, implicating RGNEF as an NFL mRNA stability regulator whose interaction is altered in ALS. Gel shift assay; IP-RT-PCR from tissue lysates; sequence homology analysis Amyotrophic lateral sclerosis Medium 19488899
2014 Two novel microRNAs (miR-b1336 and miR-b2403) downregulated in ALS spinal cord stabilize NEFL mRNA as shown by reporter gene assay and RT-PCR; anti-miR treatment confirms direct effects, demonstrating post-transcriptional regulation of NEFL mRNA stability by specific miRNAs. Small RNA library sequencing; reporter gene (luciferase) assay; quantitative RT-PCR; anti-miR functional experiments PloS one Medium 24454911
1999 βIISigma1-spectrin colocalizes with NF-L filament structures in SW13 Vim- cells transfected with full-length and C-terminal-deleted NF-L, and associates with actin; however, coimmunoprecipitation and yeast two-hybrid assays failed to demonstrate a direct NF-L–βIISigma1-spectrin interaction, suggesting an indirect association requiring a bridging protein. Transient transfection; double immunofluorescence; electron microscopy; co-immunoprecipitation; yeast two-hybrid Experimental cell research Medium 10388528
2016 Small heat shock proteins HspB1 and HspB5 (αB-crystallin) bind to NFL and modulate its assembly: HspB1 decreases NFL in pellets, shifts NFL from pellet to supernatant, binds at saturation at ~1 mol HspB1 monomer per 2 mol NFL, and slows the rate of NFL polymerization; HspB6 and HspB8 are less effective; disease-linked HspB1 point mutants (G84R, L99M, R140G, K141Q, P182S) retain similar modulation of NFL assembly. Differential centrifugation; analytical ultracentrifugation; fluorescence spectroscopy of polymerization kinetics; interaction of recombinant proteins Cell stress & chaperones High 28000086
2007 CMT-linked mutations of MTMR2 (G103E, R283W) induce NFL aggregation in SW13 vim(-) cells and impair MTMR2 dimerization and phosphorylation, while MTM1 mutations also cause NFL assembly abnormalities; this establishes that MTMR2/MTM1 are required for normal NFL filament assembly. Expression in SW13 vim(-) cells; immunofluorescence; dimerization and phosphorylation assays Journal of neurochemistry Medium 17973976
2013 NEFL mutations in different functional domains have distinct effects on filament assembly: NEFL(Q333P) causes reversible misfolding and is susceptible to HSPA1 chaperoning, while NEFL(P8R) is sensitive to HSPB1 but not HSPA1; celastrol prevents NEFL(Q333P) inclusions and mitochondrial shortening in motor neurons but not sensory neurons, and vice versa for P8R. SW13-cell filament assembly assay; in vitro refolding; chaperone induction; live neuron imaging; celastrol treatment The international journal of biochemistry & cell biology Medium 23618875
2009 In NFL-/- mice, axotomy leads to delayed and persistent cytosolic TDP-43 upregulation and sustained downregulation of neuronal PGRN, accompanied by caspase-3 activation on post-injury day 28 and subsequent neuronal death, establishing that NFL is required for normal TDP-43 localization and neuronal survival responses after axotomy. Axotomy in NFL-/- knockout mice; immunohistochemistry for TDP-43, PGRN, caspase-3; behavioral assessment Brain research Medium 19619516
2005 NFL-/- mice develop mild sensorimotor dysfunction (fewer rears, beam crossing deficits, grip failures) and spatial learning deficits in the Morris water maze by 6 months, correlated with increased cytochrome oxidase activity in cerebellum and brainstem, establishing NFL as required for normal sensorimotor and spatial function. Nefl gene knockout mice; behavioral battery (open field, stationary beam, suspended bar, Morris water maze); quantitative cytochrome oxidase histochemistry Journal of neuroscience research Medium 15884021
2018 Recessive nonsense mutations in NEFL cause nearly complete loss of NEFL mRNA via nonsense-mediated decay (NMD), leading to total absence of NEFL protein in patient-derived iPSC motor neurons, yet neurons can still differentiate and form neurofilaments, demonstrating a loss-of-function mechanism for recessive CMT; partial rescue of NEFL mRNA by NMD inhibition confirms the mechanism. iPSC-derived motor neurons; qPCR; Western blot; immunocytochemistry; electron microscopy; single-cell transcriptomics; NMD inhibitor rescue Neurology. Genetics High 29888333
1997 NF-M and NF-L mRNAs are transiently and coordinately induced in Schwann cells during Wallerian degeneration (dedifferentiation) and during early differentiation of myelin-forming Schwann cells in vivo; however, translation of these mRNAs is restricted to Schwann cells deprived of axonal contact, demonstrating axonal contact as a post-transcriptional regulator of NF-L/NF-M protein expression in Schwann cells. In situ hybridization; immunohistochemistry; Northern blot analysis of peripheral nerve at defined developmental and injury time points Journal of neuroscience research Medium 9373038
2015 miR-381 directly targets NEFL mRNA to suppress its expression; either suppressing miR-381 or overexpressing NEFL sensitizes glioblastoma cells to temozolomide by inhibiting multidrug resistance factors (ABCG2, ABCC3, ABCC5) and stemness factors (ALDH1, CD44, CKIT, KLF4, Nanog, Nestin, SOX2); NEFL-siRNA reverses NEFL-mediated TMZ sensitization. 2-D DIGE proteomics; MALDI-TOF/TOF-MS/MS; miR-381 inhibition/overexpression; NEFL overexpression/siRNA; cell viability assays; Western blot Oncotarget Medium 25605243
2015 miR-25 directly targets NEFL and suppresses its expression in glioblastoma; NEFL knockdown via siRNA attenuates the growth-inhibitory effects of miR-25 knockdown on U251 cell proliferation and invasion via the mTOR signaling pathway. miR-25 overexpression/inhibition; NEFL siRNA; cell proliferation and invasion assays; Western blot; mTOR pathway analysis Molecular and cellular biochemistry Medium 26209061
2009 In NFL-/- mice (a model of motor neuron degeneration), degenerating spinal motor neurons exhibit early upregulation of the C5a anaphylatoxin receptor (C5aR); C5a is neurotoxic to Neuro2A and NGF-differentiated PC12 cells in vitro; kainate and C5a both upregulate activated C5aR expression, suggesting C5aR upregulation in the absence of NFL potentiates excitotoxicity. NFL-/- knockout mouse immunohistochemistry; in vitro neurotoxicity assays; C5aR expression analysis Journal of neuroimmunology Medium 19286267
2013 NEFL promoter hypermethylation causes its downregulation in breast cancer cell lines and tissues; demethylation treatment restores NEFL expression in MDA-MB-231 cells, establishing promoter methylation as a mechanism of NEFL silencing in cancer. Genome-wide methylation analysis; bisulfite sequencing; RT-PCR; demethylation (5-azacytidine) rescue experiment International journal of oncology Medium 24026393

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 Blood-based NfL: A biomarker for differential diagnosis of parkinsonian disorder. Neurology 397 28179466
2015 Plasma Concentration of the Neurofilament Light Protein (NFL) is a Biomarker of CNS Injury in HIV Infection: A Cross-Sectional Study. EBioMedicine 381 26870824
2022 Plasma Aβ42/40 ratio, p-tau181, GFAP, and NfL across the Alzheimer's disease continuum: A cross-sectional and longitudinal study in the AIBL cohort. Alzheimer's & dementia : the journal of the Alzheimer's Association 233 36574591
2003 Mutations in the neurofilament light chain gene (NEFL) cause early onset severe Charcot-Marie-Tooth disease. Brain : a journal of neurology 225 12566280
2014 Neuroinflammation and brain atrophy in former NFL players: An in vivo multimodal imaging pilot study. Neurobiology of disease 192 25447235
2022 Diagnostic value of plasma p-tau181, NfL, and GFAP in a clinical setting cohort of prevalent neurodegenerative dementias. Alzheimer's research & therapy 153 36221099
1991 NF-L and peripherin immunoreactivities define distinct classes of rat sensory ganglion cells. Journal of neuroscience research 151 1795410
2022 Serum GFAP and NfL Levels Differentiate Subsequent Progression and Disease Activity in Patients With Progressive Multiple Sclerosis. Neurology(R) neuroimmunology & neuroinflammation 135 36376097
1989 Expression of NF-L and NF-M in fibroblasts reveals coassembly of neurofilament and vimentin subunits. The Journal of cell biology 119 2493000
2020 NfL as a biomarker for neurodegeneration and survival in Parkinson disease. Neurology 111 32680941
2019 Vaccination with Glycan-Modified HIV NFL Envelope Trimer-Liposomes Elicits Broadly Neutralizing Antibodies to Multiple Sites of Vulnerability. Immunity 110 31732167
2007 CSF neurofilament protein (NFL) -- a marker of active HIV-related neurodegeneration. Journal of neurology 110 17420923
2004 Mutational analysis of PMP22, MPZ, GJB1, EGR2 and NEFL in Korean Charcot-Marie-Tooth neuropathy patients. Human mutation 95 15241803
2009 A novel recessive Nefl mutation causes a severe, early-onset axonal neuropathy. Annals of neurology 89 20039262
1985 The complete amino acid sequence of the major mammalian neurofilament protein (NF-L). FEBS letters 84 3920075
2004 The novel neurofilament light (NEFL) mutation Glu397Lys is associated with a clinically and morphologically heterogeneous type of Charcot-Marie-Tooth neuropathy. Neuromuscular disorders : NMD 78 14733962
2009 Cytosolic TDP-43 expression following axotomy is associated with caspase 3 activation in NFL-/- mice: support for a role for TDP-43 in the physiological response to neuronal injury. Brain research 77 19619516
2018 CSF sAPPβ, YKL-40, and NfL along the ALS-FTD spectrum. Neurology 75 30291183
2024 Peripheral GFAP and NfL as early biomarkers for dementia: longitudinal insights from the UK Biobank. BMC medicine 73 38735950
2007 Antiretroviral treatment reduces increased CSF neurofilament protein (NFL) in HIV-1 infection. Neurology 72 17923616
2015 Targeting miR-381-NEFL axis sensitizes glioblastoma cells to temozolomide by regulating stemness factors and multidrug resistance factors. Oncotarget 71 25605243
1987 The human neurofilament gene (NEFL) is located on the short arm of chromosome 8. Cytogenetics and cell genetics 53 3036423
2019 Combined use of CSF NfL and CSF TDP-43 improves diagnostic performance in ALS. Annals of clinical and translational neurology 50 31742901
2016 NFL-lipid nanocapsules for brain neural stem cell targeting in vitro and in vivo. Journal of controlled release : official journal of the Controlled Release Society 50 27503706
2022 High or increasing serum NfL is predictive of impending multiple sclerosis relapses. Multiple sclerosis and related disorders 49 35078125
2021 Plasma NfL levels and longitudinal change rates in C9orf72 and GRN-associated diseases: from tailored references to clinical applications. Journal of neurology, neurosurgery, and psychiatry 49 34349004
2020 CSF NFL in a Longitudinally Assessed PD Cohort: Age Effects and Cognitive Trajectories. Movement disorders : official journal of the Movement Disorder Society 47 32445500
2020 A Score Based on NfL and Glial Markers May Differentiate Between Relapsing-Remitting and Progressive MS Course. Frontiers in neurology 46 32765393
2009 Neurofilament subunit (NFL) head domain phosphorylation regulates axonal transport of neurofilaments. European journal of cell biology 46 19147253
2021 Neurofilament Light Chain (NfL) in Blood-A Biomarker Predicting Unfavourable Outcome in the Acute Phase and Improvement in the Late Phase after Stroke. Cells 43 34207058
1998 Domain- and site-specific phosphorylation of bovine NF-L by Rho-associated kinase. Biochemical and biophysical research communications 41 9571164
2018 Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage. Frontiers in immunology 39 30065725
2021 Stratifying the Presymptomatic Phase of Genetic Frontotemporal Dementia by Serum NfL and pNfH: A Longitudinal Multicentre Study. Annals of neurology 38 34743360
2015 miR-25 promotes glioblastoma cell proliferation and invasion by directly targeting NEFL. Molecular and cellular biochemistry 38 26209061
1997 Transient expression of the neurofilament proteins NF-L and NF-M by Schwann cells is regulated by axonal contact. Journal of neuroscience research 38 9373038
2007 Clinical and electrophysiological features in Charcot-Marie-Tooth disease with mutations in the NEFL gene. Archives of neurology 37 17620486
2023 Quantification and prospective evaluation of serum NfL and GFAP as blood-derived biomarkers of outcome in acute ischemic stroke patients. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 36 37113060
2023 Serum NfL and GFAP are associated with incident dementia and dementia mortality in older adults: The cardiovascular health study. Alzheimer's & dementia : the journal of the Alzheimer's Association 36 37392405
2009 The complement factor C5a receptor is upregulated in NFL-/- mouse motor neurons. Journal of neuroimmunology 36 19286267
1994 Changes in neurofilament protein NF-L and NF-H immunoreactivity following kainic acid-induced seizures. Journal of neurochemistry 36 8294936
2024 Association of Plasma Amyloid, P-Tau, GFAP, and NfL With CSF, Clinical, and Cognitive Features in Patients With Dementia With Lewy Bodies. Neurology 35 38830138
2017 Genetic and clinical characteristics of NEFL-related Charcot-Marie-Tooth disease. Journal of neurology, neurosurgery, and psychiatry 35 28501821
2014 Expanding the phenotype associated with the NEFL mutation: neuromuscular disease in a family with overlapping myopathic and neurogenic findings. JAMA neurology 35 25264603
2014 Analysis of novel NEFL mRNA targeting microRNAs in amyotrophic lateral sclerosis. PloS one 34 24454911
1991 Origin of the beta cells of the islets of Langerhans is further questioned by the expression of neuronal intermediate filament proteins, peripherin and NF-L, in the rat insulinoma RIN5F cell line. Developmental neuroscience 34 1809559
2023 Evaluation of plasma levels of NFL, GFAP, UCHL1 and tau as Parkinson's disease biomarkers using multiplexed single molecule counting. Scientific reports 33 36997567
2020 Plasma NfL and GFAP as biomarkers of spinal cord degeneration in adrenoleukodystrophy. Annals of clinical and translational neurology 31 33047897
2005 Mice with the deleted neurofilament of low molecular weight (Nefl) gene: 2. Effects on motor functions and spatial orientation. Journal of neuroscience research 31 15884021
2021 Sex Differences in Behavioral Symptoms and the Levels of Circulating GFAP, Tau, and NfL in Patients With Traumatic Brain Injury. Frontiers in pharmacology 30 34899299
2015 Reduced neurofilament expression in cutaneous nerve fibers of patients with CMT2E. Neurology 30 26109717
2006 14-3-3 protein binds to the low molecular weight neurofilament (NFL) mRNA 3' UTR. Molecular and cellular neurosciences 30 17098443
2003 The nNOS inhibitor, AR-R17477AR, prevents the loss of NF68 immunoreactivity induced by methamphetamine in the mouse striatum. Journal of neurochemistry 30 12675928
2023 Associations of plasma NfL, GFAP, and t-tau with cerebral small vessel disease and incident dementia: longitudinal data of the AGES-Reykjavik Study. GeroScience 29 37530894
2008 NEFL Pro22Arg mutation in Charcot-Marie-Tooth disease type 1. Journal of human genetics 29 18758688
2020 NFL and CXCL13 may reveal disease activity in clinically and radiologically stable MS. Multiple sclerosis and related disorders 28 32862040
2024 Plasma GFAP, NfL and pTau 181 detect preclinical stages of dementia. Frontiers in endocrinology 26 38654932
2022 Plasma and CSF NfL are differentially associated with biomarker evidence of neurodegeneration in a community-based sample of 70-year-olds. Alzheimer's & dementia (Amsterdam, Netherlands) 26 35280965
2021 The Cytoskeletal Elements MAP2 and NF-L Show Substantial Alterations in Different Stroke Models While Elevated Serum Levels Highlight Especially MAP2 as a Sensitive Biomarker in Stroke Patients. Molecular neurobiology 26 33931805
2018 Absence of NEFL in patient-specific neurons in early-onset Charcot-Marie-Tooth neuropathy. Neurology. Genetics 26 29888333
1995 Characterization of the rat light neurofilament (NF-L) gene promoter and identification of NGF and cAMP responsive regions. Journal of neuroscience research 26 7745611
2016 Up-Regulation of microRNA-183 Promotes Cell Proliferation and Invasion in Glioma By Directly Targeting NEFL. Cellular and molecular neurobiology 24 26879754
2010 Human low molecular weight neurofilament (NFL) mRNA interacts with a predicted p190RhoGEF homologue (RGNEF) in humans. Amyotrophic lateral sclerosis : official publication of the World Federation of Neurology Research Group on Motor Neuron Diseases 24 19488899
2023 GFAP and NfL increase during neurotoxicity from high baseline levels in pediatric CD19-CAR T-cell patients. Blood advances 23 36006611
2022 Neurochemical Monitoring of Traumatic Brain Injury by the Combined Analysis of Plasma Beta-Synuclein, NfL, and GFAP in Polytraumatized Patients. International journal of molecular sciences 23 36077033
2023 Central nervous system biomarkers GFAp and NfL associate with post-acute cognitive impairment and fatigue following critical COVID-19. Scientific reports 22 37573366
2021 Serum GFAP and NfL levels in benign relapsing-remitting multiple sclerosis. Multiple sclerosis and related disorders 22 34627002
2021 Amyotrophic lateral sclerosis: Correlations between fluid biomarkers of NfL, TDP-43, and tau, and clinical characteristics. PloS one 22 34843548
2013 Heterogeneity in the properties of NEFL mutants causing Charcot-Marie-Tooth disease results in differential effects on neurofilament assembly and susceptibility to intervention by the chaperone-inducer, celastrol. The international journal of biochemistry & cell biology 21 23618875
1992 Effect of a discrete dorsal forebrain lesion in the rat on the expression of neuronal and glial-specific genes: induction of calmodulin, NF-L, SC1, and GFAP mRNA. Journal of neuroscience research 21 1404498
1988 Localization of the 68,000-Da human neurofilament gene (NF68) using a murine cDNA probe. Genome 20 3145240
2023 A multimodal marker for cognitive functioning in multiple sclerosis: the role of NfL, GFAP and conventional MRI in predicting cognitive functioning in a prospective clinical cohort. Journal of neurology 19 37101095
2017 A novel homozygous nonsense mutation in NEFL causes autosomal recessive Charcot-Marie-Tooth disease. Neuromuscular disorders : NMD 19 29191368
2016 Interaction of small heat shock proteins with light component of neurofilaments (NFL). Cell stress & chaperones 19 28000086
2007 Multiple disease-linked myotubularin mutations cause NFL assembly defects in cultured cells and disrupt myotubularin dimerization. Journal of neurochemistry 19 17973976
2024 Serum NfL and GFAP as biomarkers of progressive neurodegeneration in TBI. Alzheimer's & dementia : the journal of the Alzheimer's Association 17 38805359
2024 GFAP and NfL as fluid biomarkers for clinical disease severity and disease progression in multiple system atrophy (MSA). Journal of neurology 17 39254698
2023 The use of liposomes functionalized with the NFL-TBS.40-63 peptide as a targeting agent to cross the in vitro blood-brain barrier and target glioblastoma cells. International journal of pharmaceutics 17 37722495
2010 Sensorimotor and cognitive function of a NEFL(P22S) mutant model of Charcot-Marie-Tooth disease type 2E. Behavioural brain research 17 21168446
2023 Emergence delirium and postoperative delirium associated with high plasma NfL and GFAP: an observational study. Frontiers in medicine 16 37576000
2020 Expression of GSK3β, PICK1, NEFL, C4, NKCC1 and Synaptophysin in peripheral blood mononuclear cells of the first-episode schizophrenia patients. Asian journal of psychiatry 16 33373836
1996 cAMP-dependent phosphorylation of neurofilament proteins NF-L and NF-M inhibits their coassembly into filaments in vitro. Biochemical and biophysical research communications 16 8670258
2022 Combined GFAP, NFL, Tau, and UCH-L1 panel increases prediction of outcomes in neonatal encephalopathy. Pediatric research 15 35273370
2021 Elevated sTREM2 and NFL levels in patients with sepsis associated encephalopathy. The International journal of neuroscience 15 33851572
2016 The Neurofilament-Derived Peptide NFL-TBS.40-63 Targets Neural Stem Cells and Affects Their Properties. Stem cells translational medicine 15 27177578
2022 Serum NfL associated with anti-NMDA receptor encephalitis. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 14 35041115
2022 Salivary S100 calcium-binding protein beta (S100B) and neurofilament light (NfL) after acute exposure to repeated head impacts in collegiate water polo players. Scientific reports 14 35236877
2025 Diagnostic performance of plasma Aβ42/40 ratio, p-tau181, GFAP, and NfL along the continuum of Alzheimer's disease and non-AD dementias: An international multi-center study. Alzheimer's & dementia : the journal of the Alzheimer's Association 13 40551285
2021 SNAIL regulates gastric carcinogenesis through CCN3 and NEFL. Carcinogenesis 13 33313663
1999 Characterization of NF-L and betaIISigma1-spectrin interaction in live cells. Experimental cell research 13 10388528
2024 Performance of biomarkers NF-L, NSE, Tau and GFAP in blood and cerebrospinal fluid in rat for the detection of nervous system injury. Frontiers in neuroscience 12 38292901
2022 Plasma tau, NfL, GFAP and UCHL1 as candidate biomarkers of alcohol withdrawal-associated brain damage: A pilot study. Addiction biology 12 36301211
2020 Increased CSF NFL in Non-demented Parkinson's Disease Subjects Reflects Early White Matter Damage. Frontiers in aging neuroscience 12 32477099
2019 A novel pathogenic variant of NEFL responsible for deafness associated with peripheral neuropathy discovered through next-generation sequencing and review of the literature. Journal of the peripheral nervous system : JPNS 12 30734407
2013 Stage-specific methylome screen identifies that NEFL is downregulated by promoter hypermethylation in breast cancer. International journal of oncology 12 24026393
2005 Mice with the deleted neurofilament of low-molecular-weight (Nefl) gene: 1. Effects on regional brain metabolism. Journal of neuroscience research 12 15742362
2025 Comparative Performances of 4 Serum NfL Assays, pTau181, and GFAP in Patients With Amyotrophic Lateral Sclerosis. Neurology 11 40009787
2023 Changes in neurofilament light chain protein (NEFL) in children and adolescents with Schizophrenia and Bipolar Disorder: Early period neurodegeneration. Journal of psychiatric research 11 37003244
2022 Phenotypic heterogeneity in patients with NEFL-related Charcot-Marie-Tooth disease. Molecular genetics & genomic medicine 11 35044100
2022 Plasma Cystatin C Correlates with Plasma NfL Levels and Predicts Disease Progression in Parkinson's Disease. Neuro-degenerative diseases 11 35287127
2022 MiR-30b-5p attenuates the inflammatory response and facilitates the functional recovery of spinal cord injury by targeting the NEFL/mTOR pathway. Brain and behavior 11 36282532