Affinage

NEFL

Neurofilament light polypeptide · UniProt P07196

Length
543 aa
Mass
61.5 kDa
Annotated
2026-06-10
100 papers in source corpus 24 papers cited in narrative 23 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

NEFL encodes the light subunit of neuronal neurofilaments, an intermediate filament protein that assembles into the axonal cytoskeleton and is the principal determinant of axonal caliber (PMID:2493000, PMID:20039262). The NF-L subunit is intrinsically competent to polymerize into intermediate filament arrays, copolymerizing with vimentin in non-neuronal cells and forming filaments without requiring neuron-specific factors (PMID:2493000); it marks a discrete population of large-caliber neurons distinct from peripherin-expressing small neurons (PMID:1795410). Assembly and axonal transport of neurofilaments are negatively regulated by phosphorylation of the NF-L head domain, where phosphomimetic substitutions inhibit both transport and filament formation (PMID:19147253), and by small heat-shock proteins HspB1 and HspB5, which bind NF-L and retard its polymerization from tetramers to filaments (PMID:28000086). NEFL mRNA abundance is governed post-transcriptionally by a 3'UTR-binding regulatory network: 14-3-3 isoforms bind hexanucleotide motifs, while TDP-43 engages UG-motif stem loops through its RRM1/RRM2 domains and acts together with 14-3-3 and SOD1 to modulate transcript stability; in ALS motor neurons this mRNA is pathologically sequestered into TDP-43-positive stress granules and P-bodies (PMID:17098443, PMID:19815002). Dominant missense mutations in NEFL cause Charcot-Marie-Tooth neuropathy (CMT2E/CMT1F) by disrupting the neurofilament network and inducing NF-L aggregation, a mechanism shared with HSPB1 mutations and reversible by chaperone activity (PMID:12566280, PMID:17881652), whereas homozygous nonsense mutations cause a recessive loss-of-function neuropathy via nonsense-mediated decay and complete absence of NF-L protein (PMID:20039262, PMID:29888333). In cancer, NEFL behaves as a tumor suppressor silenced by oncogenic miRNAs (miR-381, miR-25, miR-183) and positioned upstream of mTOR signaling (PMID:25605243, PMID:26209061, PMID:26879754).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1989 High

    Established that NF-L is an autonomous intermediate filament-forming subunit, answering whether neuron-specific machinery is required for neurofilament assembly.

    Evidence Stable transfection of NF-L into non-neuronal L cells with immunofluorescence and vimentin co-fractionation

    PMID:2493000

    Open questions at the time
    • Does not address obligate heteropolymer requirements with NF-M/NF-H in neurons
    • Vimentin copolymerization is a non-neuronal context
  2. 1991 High

    Defined NF-L as a marker distinguishing large-caliber neurons from peripherin-positive small neurons, linking subunit expression to neuronal cell identity.

    Evidence Double immunofluorescence on rat DRG with neuropeptide co-localization

    PMID:1795410

    Open questions at the time
    • Correlative classification, not mechanistic
    • Does not explain caliber control
  3. 1995 High

    Mapped transcriptional control elements of the NF-L gene, showing NGF- and cAMP-responsive regulation of its promoter.

    Evidence Serial promoter deletion CAT reporter assays in PC12 cells; DNase I hypersensitivity mapping

    PMID:7745611

    Open questions at the time
    • Identifies responsive regions but not all bound transcription factors
    • Rat promoter; human conservation not addressed
  4. 2003 High

    Identified NEFL as a CMT disease gene, establishing that dominant mutations cause axonal neuropathy.

    Evidence Mutation screening of 323 CMT patients by direct sequencing with sural nerve biopsy

    PMID:12566280

    Open questions at the time
    • Genotype identified but molecular consequences of each mutation not dissected
  5. 2006 High

    Revealed post-transcriptional control of NFL mRNA stability by 14-3-3 proteins binding the 3'UTR, opening a regulatory layer beyond transcription.

    Evidence LC/MS/MS of 3'UTR-interacting proteins, gel shift, and motif mutagenesis from human spinal cord

    PMID:17098443

    Open questions at the time
    • In vitro binding; physiological stability changes not quantified in neurons
    • Functional consequence of each isoform unresolved
  6. 2007 High

    Demonstrated a shared pathogenic pathway between NFL and HSPB1 CMT mutations centered on NFL aggregation, and a chaperone role for HspB1.

    Evidence Motor neuron culture, co-expression, Co-IP, NFL deletion rescue, and viability assays

    PMID:17881652

    Open questions at the time
    • Mechanism of HspB1-mediated disaggregation not resolved at structural level
  7. 2007 Medium

    Extended mutational converging on NFL misassembly to MTMR2/MTM1, linking myotubularin dimerization defects to neurofilament abnormalities.

    Evidence SW13vim(-) transfection assembly assay with MTMR2 dimerization and phosphorylation analysis

    PMID:17973976

    Open questions at the time
    • Cell-line based, single lab
    • Direct biochemical link between myotubularin and NFL not shown
  8. 2009 High

    Showed head-domain phosphorylation governs neurofilament assembly and axonal transport, defining a post-translational switch.

    Evidence Phosphoablation and phosphomimetic mutagenesis of four head-domain sites with axonal transport readout

    PMID:19147253

    Open questions at the time
    • Responsible kinases not identified in this corpus
    • In vivo physiological relevance not established
  9. 2009 High

    Defined the TDP-43/14-3-3/SOD1 mRNA-stability network and its pathological redistribution into stress granules and P-bodies in ALS.

    Evidence Ex vivo stability assays, RNA-IP-PCR, TDP-43 RRM mutagenesis, and immunofluorescence co-localization

    PMID:19815002

    Open questions at the time
    • Causal direction between mRNA sequestration and neurodegeneration unresolved
  10. 2009 High

    Established a recessive loss-of-function mechanism via a homozygous nonsense mutation, confirming neurofilaments as the main determinant of axonal caliber.

    Evidence SW13vim(-) filament assays, sural nerve biopsy EM, and homozygosity mapping

    PMID:20039262

    Open questions at the time
    • mRNA fate of the nonsense allele not yet defined at this stage
  11. 2010 Medium

    Added RGNEF as a disease-state-dependent NFL mRNA-binding protein detectable in ALS but not control tissue.

    Evidence Gel shift assays in vitro and in tissue lysates with IP-RT-PCR

    PMID:19488899

    Open questions at the time
    • Functional effect on mRNA stability not measured
    • Single lab
  12. 2013 Medium

    Showed CMT NEFL mutations differ in misfolding behavior and chaperone susceptibility, refining therapeutic chaperone strategies.

    Evidence SW13vim(-) assays, in vitro refolding, and celastrol/chaperone induction in motor and sensory neurons

    PMID:23618875

    Open questions at the time
    • Single lab
    • Cell-type-specific chaperone responses mechanistically unexplained
  13. 2014 Medium

    Identified ALS-downregulated miRNAs that stabilize NEFL mRNA, expanding the mRNA-stability regulatory layer.

    Evidence Small RNA sequencing, luciferase reporter, and anti-miR functional assays

    PMID:24454911

    Open questions at the time
    • Novel miRNAs uncharacterized beyond this study
    • Single lab
  14. 2015 Medium

    Defined a tumor-suppressor role for NEFL silenced by miR-381, linking its loss to chemoresistance and stemness in glioblastoma.

    Evidence 2-D DIGE/MS identification with miR-381 and NEFL gain/loss-of-function and TMZ viability assays

    PMID:25605243

    Open questions at the time
    • Mechanism by which NEFL suppresses resistance factors not resolved
  15. 2015 Medium

    Placed NEFL upstream of mTOR signaling via miR-25, connecting its loss to glioblastoma proliferation and invasion.

    Evidence miR-25 gain/loss and NEFL siRNA rescue with mTOR pathway analysis in U251 cells

    PMID:26209061

    Open questions at the time
    • Molecular link between NEFL and mTOR not biochemically defined
    • Single lab
  16. 2015 High

    Demonstrated in CMT2E patient tissue that reduced neurofilament abundance, not aggregation, correlates with reduced axonal caliber.

    Evidence Skin biopsy IF, Western blot, EM, and axonal caliber morphometry

    PMID:26109717

    Open questions at the time
    • Single mutation (E396K); generalizability across CMT alleles not shown
  17. 2016 High

    Quantified the biochemical chaperone interaction, showing HspB1 and HspB5 bind NFL and slow tetramer-to-filament polymerization.

    Evidence Differential centrifugation, analytical ultracentrifugation, and fluorescent polymerization assays with stoichiometry

    PMID:28000086

    Open questions at the time
    • In vitro reconstitution; in-cell relevance of stoichiometry not addressed
  18. 2016 Medium

    Added miR-183 to the oncomiR set repressing NEFL upstream of mTOR in glioblastoma.

    Evidence miR-183 gain/loss and NEFL siRNA rescue with mTOR analysis in U251 cells

    PMID:26879754

    Open questions at the time
    • Direct NEFL-mTOR molecular link unresolved
    • Single lab
  19. 2018 High

    Established that the recessive nonsense allele triggers nonsense-mediated decay, proving a true loss-of-function mechanism in patient-derived neurons.

    Evidence iPSC-derived motor neurons, qPCR, Western blot, ICC, EM, scRNA-seq, and NMD inhibitor rescue

    PMID:29888333

    Open questions at the time
    • Why neurons still form networks without NF-L not mechanistically explained
  20. 2022 Medium

    Extended the NEFL-mTOR axis to spinal cord injury, with miR-30b-5p repression of NEFL modulating inflammation and recovery.

    Evidence Dual-luciferase reporter, NEFL silencing in PC12 cells, and SCI rat model with mTOR analysis

    PMID:36282532

    Open questions at the time
    • Single lab
    • NEFL-mTOR coupling mechanism still undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular mechanism by which cytoplasmic NEFL activates mTOR signaling and acts as a tumor suppressor remains undefined.
  • No biochemical link between NF-L and mTOR pathway components identified
  • Kinases controlling head-domain phosphorylation not identified in this corpus
  • Structural basis of chaperone-mediated assembly control unresolved

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 2 GO:0005829 cytosol 1
Pathway
R-HSA-1643685 Disease 4 R-HSA-162582 Signal Transduction 3 R-HSA-8953854 Metabolism of RNA 2
Partners
HSPB1HSPB5NEFMRGNEFSOD1TARDBPVIMYWHAZ
Complex memberships
neurofilament

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 expressed in non-neuronal fibroblasts (L cells) were efficiently assembled into intermediate filament arrays, demonstrating competence of both subunits to assemble in vivo without neuron-specific factors. NF-L-containing filaments appeared to be copolymers with vimentin, as evidenced by altered solubility of endogenous vimentin filaments. Stable DNA transfection into L cells; immunofluorescence localization; vimentin solubility co-fractionation The Journal of cell biology High 2493000
1991 Immunofluorescence of rat dorsal root ganglia identified three neuronal subpopulations defined by NF-L and peripherin expression: large NF-L-positive/peripherin-negative neurons and small peripherin-positive/NF-L-negative neurons, with a minor dual-positive population. NF-L-positive large neurons rarely contained neuropeptides, whereas peripherin-positive small neurons predominantly expressed substance P and CGRP. Double immunofluorescence with antibodies against NF-L and peripherin on rat DRG sections; neuropeptide co-localization Journal of neuroscience research High 1795410
1995 Characterization of the rat NF-L gene promoter identified basic promoter activity between -407 and +75 bp, an NGF-responsive element between -38 and +75 bp, and a functional cAMP-responsive element between -97 and -38 bp. NGF treatment of PC12 cells stimulated NF-L promoter-driven CAT expression up to 12-fold, while EGF had no effect. Reporter gene (CAT) transfection assays with serial promoter deletion constructs in PC12 and non-neural cell lines; DNase I hypersensitivity mapping; transcription factor binding assays Journal of neuroscience research High 7745611
2003 Mutations in functionally defined domains of the NEFL protein (six missense mutations and one 3-bp in-frame deletion) cause autosomal dominant Charcot-Marie-Tooth neuropathy (CMT2E/CMT1F), with nerve biopsy showing axonal pathology including axonal regeneration clusters and onion bulb formations. Mutation screening of 323 CMT patients by direct sequencing; sural nerve biopsy with histopathology Brain : a journal of neurology High 12566280
2006 14-3-3 proteins (beta, zeta, tau, gamma, and eta isoforms) bind directly to the NFL mRNA 3' UTR via two hexanucleotide motifs. Mutation of one or both motifs decreased 14-3-3 interaction, altered predicted mRNA structure, and changed mRNA stability, establishing 14-3-3 as a novel regulator of NFL mRNA stability. LC/MS/MS of NFL 3'UTR-interacting proteins from human spinal cord; in vitro expression of isoforms; gel shift assay; 3'UTR motif mutagenesis Molecular and cellular neurosciences High 17098443
2007 CMT2E-linked NFL mutations and CMT2F-linked HSPB1 (S135F) mutations share a common pathogenic pathway: disruption of the neurofilament network with aggregation of NFL protein leads to progressive motor neuron degeneration. Wild-type HSPB1 physically associates with NFL, can reverse CMT mutant NFL aggregates, and reduces CMT mutant NFL-induced motor neuron death. Deletion of NFL markedly reduces degeneration caused by S135F HSPB1. Motor neuron culture; co-expression of mutant and wild-type proteins; co-immunoprecipitation (HSPB1–NFL association); loss-of-function (NFL deletion); cell viability assays Human molecular genetics High 17881652
2007 CMT-linked mutations in MTMR2 (G103E, R283W) cause NFL aggregation in SW13vim(-) cells lacking endogenous intermediate filaments, and mutations in MTM1 also induce NFL abnormalities in these cells. MTMR2 mutants G103E and R283W are unable to form dimers and undergo phosphorylation in vivo, implicating impaired myotubularin complex formation in NFL misassembly. Transfection of SW13vim(-) cells; immunofluorescence for NFL aggregation; in vivo phosphorylation and dimerization assays for MTMR2 mutants Journal of neurochemistry Medium 17973976
2009 TDP-43 binds NFL mRNA 3'UTR via ribonucleotide (UG) motifs on stem loops, using its RRM1 and RRM2 motifs. Ex vivo, TDP-43, 14-3-3, and SOD1 interact to modulate NFL mRNA stability. In ALS motor neurons, NFL mRNA is preferentially sequestered to stress granules (TIA-1-positive) and processing bodies (P-bodies; XRN-1-positive) that co-localize with TDP-43, whereas these compartments are more prevalent in ALS than in control neurons. Ex vivo mRNA stability assays; RNA-immunoprecipitation-PCR; immunofluorescence co-localization; TDP-43 domain mutagenesis (RRM1/RRM2) Brain research High 19815002
2009 Phosphorylation of NFL head domain regulates neurofilament axonal transport. Mutation of three or four head domain phosphorylation sites to phosphomimetic residues inhibited axonal transport and disrupted neurofilament assembly, while precluding phosphorylation at those sites had no effect on transport. Site-directed mutagenesis of four phosphorylation sites in NFL head domain; monitoring of axonal transport of phosphorylation mutants in neurons European journal of cell biology High 19147253
2009 A homozygous nonsense mutation (E210X) in NEFL causes autosomal recessive, severe early-onset axonal neuropathy. The E210X mutant protein fails to form an intermediate filament network in SW13vim(-) cells but does not interfere with filament formation by wild-type NEFL. Sural nerve biopsy from an affected patient confirmed absence of intermediate filaments in remaining myelinated axons and smaller axonal caliber, consistent with neurofilaments being the main determinant of axonal caliber. SW13vim(-) cell transfection assay for filament-forming ability; sural nerve biopsy with electron microscopy and immunohistochemistry; genetic analysis (homozygosity mapping) Annals of neurology High 20039262
2010 Human RGNEF (a homologue of mouse p190RhoGEF) binds NFL mRNA in vitro via gel shift assay, and this interaction is detectable in ALS tissue lysates but not in control lysates, suggesting that the RGNEF–NFL mRNA interaction is disease-state dependent. Gel shift assays (in vitro and in tissue lysates); IP-RT-PCR; RT-PCR expression analysis in ALS and control spinal cord Amyotrophic lateral sclerosis Medium 19488899
2013 NEFL mutations in different functional domains of the protein have heterogeneous effects on neurofilament assembly and chaperone susceptibility: Q333P causes reversible misfolding and forms coiled-coil dimers in vitro; it can be refolded by chaotropic agent and its aggregation in motor neurons prevented by HSPA1 induction by celastrol. P8R is sensitive to HSPB1 but not HSPA1 chaperoning, and celastrol is protective against P8R toxicity only in large sensory neurons, not motor neurons. SW13vim(-) cell transfection assay; in vitro refolding with chaotropic agents; celastrol treatment of cultured motor and sensory neurons; chaperone induction assays The international journal of biochemistry & cell biology Medium 23618875
2014 Two novel miRNAs (miR-b1336 and miR-b2403) are downregulated in ALS spinal cord and stabilize NEFL mRNA, as demonstrated by reporter gene assay and RT-PCR; inhibition with anti-miRs further confirmed their role in NEFL mRNA stability. Small RNA library sequencing from ALS and control spinal cords; real-time PCR; reporter gene (luciferase) assay; anti-miR functional assays PloS one Medium 24454911
2015 miR-381 directly targets NEFL (identified by 2-D DIGE, MALDI-TOF/TOF-MS/MS, and functional validation); suppressing miR-381 or enforcing NEFL expression sensitizes glioblastoma cells to temozolomide by inhibiting multidrug resistance factors (ABCG2, ABCC3, ABCC5) and stemness factors (ALDH1, CD44, SOX2, etc.). NEFL-siRNA reverses the TMZ sensitization caused by LNA-anti-miR-381. 2-D DIGE and mass spectrometry protein identification; miR-381 overexpression/inhibition; NEFL overexpression and siRNA knockdown; cell viability assays; Western blot Oncotarget Medium 25605243
2015 miR-25 directly targets NEFL in glioblastoma cells; miR-25 overexpression promotes and its antisense oligos inhibit cell proliferation and invasion. NEFL-siRNA attenuates the inhibitory effects of miR-25 knockdown on proliferation and invasion via the mTOR signaling pathway. miR-25 overexpression/knockdown in U251 cells; NEFL siRNA; proliferation and invasion assays; mTOR pathway analysis Molecular and cellular biochemistry Medium 26209061
2015 In CMT2E patients carrying NEFL Glu396Lys mutation, skin biopsy showed markedly reduced or absent neurofilament (NF) proteins in axons by immunofluorescence and Western blot, with normal α-tubulin expression. Electron microscopy confirmed absence of NF aggregates in dermal axons and smaller axonal caliber, demonstrating that decreased NF abundance (not aggregation) correlates with reduced axonal caliber in CMT2E. Skin biopsy; indirect immunofluorescence; Western blot; electron microscopy; morphometric analysis of axonal caliber Neurology High 26109717
2016 Human small heat shock protein HspB1 physically associates with NFL and modulates NFL assembly: wild-type HspB1 decreased the quantity of NFL in pellets and increased NFL in supernatant. HspB1 decreased the rate of NFL polymerization from tetramers to filaments. At saturation, ~1 mol HspB1 monomer bound per 2 mol NFL. HspB5 (αB-crystallin) also decreased NFL polymerization rate, while HspB6 and HspB8 were less effective. Differential centrifugation; analytical ultracentrifugation; fluorescent spectroscopy of NFL polymerization; binding stoichiometry determination Cell stress & chaperones High 28000086
2018 Patient-specific iPSC-derived motor neurons carrying a homozygous nonsense NEFL mutation showed nearly total loss of NEFL mRNA by qPCR, leading to complete absence of NEFL protein by immunocytochemistry and Western blot. Nonsense-mediated decay (NMD) caused the mRNA loss, as NMD inhibition partially rescued NEFL mRNA. Neurons still formed neurofilaments and neuronal networks in the absence of NEFL, indicating the recessive mechanism is loss-of-function. iPSC differentiation to motor neurons; qPCR; Western blot; immunocytochemistry; electron microscopy; single-cell transcriptomics; NMD inhibitor treatment Neurology. Genetics High 29888333
2016 miR-183 directly targets NEFL in glioblastoma cells; miR-183 overexpression promotes and its antisense oligos inhibit cell proliferation and invasion in U251 cells. NEFL-siRNA attenuates the inhibitory effects of miR-183 knockdown via the mTOR signaling pathway. miR-183 overexpression/knockdown in glioblastoma cells; NEFL siRNA; proliferation and invasion assays; mTOR pathway analysis Cellular and molecular neurobiology Medium 26879754
2005 NFL-deficient mice (NFL-/-) develop transient NF aggregates in motor neurons, reactive microgliosis, progressive motor neuron loss, significant astrogliosis, and HSP-70 upregulation in motor neurons and astrocytes. In contrast, hNFL(+/+) overexpression mice showed NF aggregates and microgliosis but no significant astrogliosis. This indicates that the etiology of NF aggregate formation determines the glial response pattern. Longitudinal histological analysis of transgenic mice (1–18 months); immunohistochemistry for microglia, astrocytes, and HSP-70; motor neuron counting Glia Medium 15920739
2022 MiR-30b-5p directly targets NEFL mRNA (confirmed by dual-luciferase reporter gene assay), negatively regulating its mRNA and protein levels. NEFL activates mTOR signaling. In SCI cell and rat models, miR-30b-5p inactivates mTOR signaling by negatively regulating NEFL, thereby attenuating the inflammatory response and facilitating functional recovery. Dual-luciferase reporter assay; RT-qPCR and Western blot; NEFL silencing in LPS-stimulated PC12 cells; SCI rat model; mTOR pathway analysis Brain and behavior Medium 36282532
1987 The human neurofilament light chain gene (NEFL) was localized to chromosome band 8p21 by Southern blotting of hybrid cell panels and in situ hybridization to metaphase chromosomes. Southern blotting of somatic cell hybrid panels; in situ hybridization to metaphase chromosomes Cytogenetics and cell genetics High 3036423 3145240
2021 SNAIL regulates NEFL expression in gastric cancer: microarray analysis after SNAIL knockdown in HGC27 cells identified NEFL as one of the most downregulated genes. Upregulation of NEFL or downregulation of CCN3 impaired SNAIL-dependent EMT activity (tumorigenicity, chemoresistance), placing NEFL in the SNAIL/CCN3/NEFL axis governing gastric cancer stemness. Microarray analysis; SNAIL knockdown; NEFL modulation; tumorigenicity and chemoresistance assays in gastric cancer cell lines and gastric oncospheres Carcinogenesis Low 33313663

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 404 28179466
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 243 36574591
2003 Mutations in the neurofilament light chain gene (NEFL) cause early onset severe Charcot-Marie-Tooth disease. Brain : a journal of neurology 227 12566280
2014 Neuroinflammation and brain atrophy in former NFL players: An in vivo multimodal imaging pilot study. Neurobiology of disease 193 25447235
2020 Time course and diagnostic utility of NfL, tau, GFAP, and UCH-L1 in subacute and chronic TBI. Neurology 187 32641529
2009 Tar DNA binding protein of 43 kDa (TDP-43), 14-3-3 proteins and copper/zinc superoxide dismutase (SOD1) interact to modulate NFL mRNA stability. Implications for altered RNA processing in amyotrophic lateral sclerosis (ALS). Brain research 179 19815002
2022 Diagnostic value of plasma p-tau181, NfL, and GFAP in a clinical setting cohort of prevalent neurodegenerative dementias. Alzheimer's research & therapy 163 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 142 36376097
2019 NFL is a marker of treatment response in children with SMA treated with nusinersen. Journal of neurology 128 31123861
1989 Expression of NF-L and NF-M in fibroblasts reveals coassembly of neurofilament and vimentin subunits. The Journal of cell biology 120 2493000
2019 NfL (Neurofilament Light Chain) Levels as a Predictive Marker for Long-Term Outcome After Ischemic Stroke. Stroke 118 31537188
2020 NfL as a biomarker for neurodegeneration and survival in Parkinson disease. Neurology 112 32680941
2007 CSF neurofilament protein (NFL) -- a marker of active HIV-related neurodegeneration. Journal of neurology 110 17420923
2007 Disruption of neurofilament network with aggregation of light neurofilament protein: a common pathway leading to motor neuron degeneration due to Charcot-Marie-Tooth disease-linked mutations in NFL and HSPB1. Human molecular genetics 96 17881652
2009 A novel recessive Nefl mutation causes a severe, early-onset axonal neuropathy. Annals of neurology 91 20039262
2024 Peripheral GFAP and NfL as early biomarkers for dementia: longitudinal insights from the UK Biobank. BMC medicine 84 38735950
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
2018 CSF sAPPβ, YKL-40, and NfL along the ALS-FTD spectrum. Neurology 75 30291183
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 52 31742901
2022 High or increasing serum NfL is predictive of impending multiple sclerosis relapses. Multiple sclerosis and related disorders 51 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 51 34349004
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
2020 CSF NFL in a Longitudinally Assessed PD Cohort: Age Effects and Cognitive Trajectories. Movement disorders : official journal of the Movement Disorder Society 48 32445500
2020 A Score Based on NfL and Glial Markers May Differentiate Between Relapsing-Remitting and Progressive MS Course. Frontiers in neurology 48 32765393
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 46 34207058
2009 Neurofilament subunit (NFL) head domain phosphorylation regulates axonal transport of neurofilaments. European journal of cell biology 46 19147253
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 41 37113060
2024 Association of Plasma Amyloid, P-Tau, GFAP, and NfL With CSF, Clinical, and Cognitive Features in Patients With Dementia With Lewy Bodies. Neurology 40 38830138
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 40 37392405
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
2007 Clinical and electrophysiological features in Charcot-Marie-Tooth disease with mutations in the NEFL gene. Archives of neurology 37 17620486
2017 Genetic and clinical characteristics of NEFL-related Charcot-Marie-Tooth disease. Journal of neurology, neurosurgery, and psychiatry 36 28501821
2014 Expanding the phenotype associated with the NEFL mutation: neuromuscular disease in a family with overlapping myopathic and neurogenic findings. JAMA neurology 36 25264603
2023 Evaluation of plasma levels of NFL, GFAP, UCHL1 and tau as Parkinson's disease biomarkers using multiplexed single molecule counting. Scientific reports 35 36997567
2022 Effect of Estimated Blood Volume and Body Mass Index on GFAP and NfL Levels in the Serum and CSF of Patients With Multiple Sclerosis. Neurology(R) neuroimmunology & neuroinflammation 35 36316116
2014 Analysis of novel NEFL mRNA targeting microRNAs in amyotrophic lateral sclerosis. PloS one 34 24454911
2020 Plasma NfL and GFAP as biomarkers of spinal cord degeneration in adrenoleukodystrophy. Annals of clinical and translational neurology 32 33047897
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 31 37530894
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
2018 New MiniPromoter Ple345 (NEFL) Drives Strong and Specific Expression in Retinal Ganglion Cells of Mouse and Primate Retina. Human gene therapy 30 30062914
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
2024 Plasma GFAP, NfL and pTau 181 detect preclinical stages of dementia. Frontiers in endocrinology 29 38654932
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
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) 27 35280965
2022 Serum NfL but not GFAP predicts cognitive decline in active progressive multiple sclerosis patients. Multiple sclerosis (Houndmills, Basingstoke, England) 27 36448331
2018 Absence of NEFL in patient-specific neurons in early-onset Charcot-Marie-Tooth neuropathy. Neurology. Genetics 27 29888333
2013 The NFL-TBS.40-63 anti-glioblastoma peptide enters selectively in glioma cells by endocytosis. International journal of pharmaceutics 27 23603097
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
2023 GFAP and NfL increase during neurotoxicity from high baseline levels in pediatric CD19-CAR T-cell patients. Blood advances 25 36006611
2023 Central nervous system biomarkers GFAp and NfL associate with post-acute cognitive impairment and fatigue following critical COVID-19. Scientific reports 25 37573366
2016 Up-Regulation of microRNA-183 Promotes Cell Proliferation and Invasion in Glioma By Directly Targeting NEFL. Cellular and molecular neurobiology 25 26879754
2015 NEFL N98S mutation: another cause of dominant intermediate Charcot-Marie-Tooth disease with heterogeneous early-onset phenotype. Journal of neurology 25 26645395
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 25 19488899
2021 Amyotrophic lateral sclerosis: Correlations between fluid biomarkers of NfL, TDP-43, and tau, and clinical characteristics. PloS one 23 34843548
2015 NEFL E396K mutation is associated with a novel dominant intermediate Charcot-Marie-Tooth disease phenotype. Journal of neurology 23 25877835
2021 Serum GFAP and NfL levels in benign relapsing-remitting multiple sclerosis. Multiple sclerosis and related disorders 22 34627002
2024 Serum NfL and GFAP as biomarkers of progressive neurodegeneration in TBI. Alzheimer's & dementia : the journal of the Alzheimer's Association 21 38805359
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
2013 The role of NEFL in cell growth and invasion in head and neck squamous cell carcinoma cell lines. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 21 23992471
2017 A novel homozygous nonsense mutation in NEFL causes autosomal recessive Charcot-Marie-Tooth disease. Neuromuscular disorders : NMD 20 29191368
1988 Localization of the 68,000-Da human neurofilament gene (NF68) using a murine cDNA probe. Genome 20 3145240
2024 GFAP and NfL as fluid biomarkers for clinical disease severity and disease progression in multiple system atrophy (MSA). Journal of neurology 19 39254698
2023 Emergence delirium and postoperative delirium associated with high plasma NfL and GFAP: an observational study. Frontiers in medicine 19 37576000
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
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 17 40551285
2024 Evaluating the utility of serum NfL, GFAP, UCHL1 and tTAU as estimates of CSF levels and diagnostic instrument in neuroinflammation and multiple sclerosis. Multiple sclerosis and related disorders 17 38701697
2022 Combined GFAP, NFL, Tau, and UCH-L1 panel increases prediction of outcomes in neonatal encephalopathy. Pediatric research 17 35273370
2010 Sensorimotor and cognitive function of a NEFL(P22S) mutant model of Charcot-Marie-Tooth disease type 2E. Behavioural brain research 17 21168446
2005 Temporal profiles of neuronal degeneration, glial proliferation, and cell death in hNFL(+/+) and NFL(-/-) mice. Glia 17 15920739
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
2025 Comparative Performances of 4 Serum NfL Assays, pTau181, and GFAP in Patients With Amyotrophic Lateral Sclerosis. Neurology 15 40009787
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 15 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 15 35236877
2021 SNAIL regulates gastric carcinogenesis through CCN3 and NEFL. Carcinogenesis 15 33313663
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
2025 The role of Neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) in MS and AQP4-NMOSD: Advancing clinical applications. eNeurologicalSci 14 39866832
2025 Plasma NfL and GFAP for predicting VCI and related brain changes in community and clinical cohorts. Alzheimer's & dementia : the journal of the Alzheimer's Association 13 40566826
2022 Plasma tau, NfL, GFAP and UCHL1 as candidate biomarkers of alcohol withdrawal-associated brain damage: A pilot study. Addiction biology 13 36301211
2020 Increased CSF NFL in Non-demented Parkinson's Disease Subjects Reflects Early White Matter Damage. Frontiers in aging neuroscience 13 32477099
2009 The neurofilament light chain gene (NEFL) mutation Pro22Ser can be associated with mixed axonal and demyelinating neuropathy. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 13 19286384
2023 Changes in neurofilament light chain protein (NEFL) in children and adolescents with Schizophrenia and Bipolar Disorder: Early period neurodegeneration. Journal of psychiatric research 12 37003244
2022 Phenotypic heterogeneity in patients with NEFL-related Charcot-Marie-Tooth disease. Molecular genetics & genomic medicine 12 35044100
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
2005 Mice with the deleted neurofilament of low-molecular-weight (Nefl) gene: 1. Effects on regional brain metabolism. Journal of neuroscience research 12 15742362
2024 Serum GFAP, NfL, and tau concentrations are associated with worse neurobehavioral functioning following mild, moderate, and severe TBI: a cross-sectional multiple-cohort study. Frontiers in neurology 11 38292036
2024 An exploratory study of the damage markers NfL, GFAP, and t-Tau, in cerebrospinal fluid and other findings from a patient cohort enriched for suspected autoimmune psychiatric disease. Translational psychiatry 11 39048548
2023 NfL and GFAP in serum are associated with microstructural brain damage in progressive multiple sclerosis. Multiple sclerosis and related disorders 11 37418931
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
2024 Novel Genetic and Biochemical Insights into the Spectrum of NEFL-Associated Phenotypes. Journal of neuromuscular diseases 10 38578900

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