Affinage

NGFR

Tumor necrosis factor receptor superfamily member 16 · UniProt P08138

Length
427 aa
Mass
45.2 kDa
Annotated
2026-04-29
100 papers in source corpus 32 papers cited in narrative 32 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NGFR (p75NTR) is a TNFR superfamily receptor that functions as a signaling hub integrating neurotrophin-dependent survival, apoptosis, differentiation, and axon guidance by assembling context-specific co-receptor complexes and recruiting distinct intracellular adaptors. It forms ligand-modulated complexes with TrkA/B/C to sharpen neurotrophin specificity (PMID:9927421), with NgR to transduce myelin-associated inhibitory signals (PMID:12426574), and with sortilin to mediate proNGF/proBDNF-induced apoptosis via a JNK–Bad cascade requiring the adaptor NRAGE (PMID:14673001, PMID:18772898, PMID:20036257); it also engages Rho GTPases for differentiation and motility (PMID:17395831), a Rac1–PI4K–PIP2 pathway that modulates neuronal excitability (PMID:26134656), and neutral sphingomyelinase-derived ceramide signaling that promotes amyloidogenic APP processing (PMID:15966860, PMID:33258176). Phosphorylation of Ser266 by cPKC delays endosomal sorting to prolong death signaling (PMID:19710323), while PKA-dependent Ser303 phosphorylation creates a PDZ-binding motif that recruits PDLIM1 to drive glioma invasion (PMID:26119933); in melanoma, NGFR confers immune evasion by upregulating stearoyl-CoA desaturase to suppress NK cell recognition and by inducing BDNF-mediated T cell resistance (PMID:36638181, PMID:32770055, PMID:34957415).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1999 High

    Establishing that p75NTR physically associates with all three Trk receptors and sharpens their ligand specificity answered how a receptor lacking intrinsic kinase activity could modulate neurotrophin signaling fidelity.

    Evidence Co-immunoprecipitation with domain-deletion constructs and ligand-specificity assays in co-transfected cells

    PMID:9927421

    Open questions at the time
    • Stoichiometry of the p75NTR–Trk complex unresolved
    • Whether the association occurs with endogenous proteins in neurons was not directly tested
    • Structural basis of the extracellular vs. intracellular domain interaction unknown
  2. 2002 High

    Demonstrating that p75NTR serves as the signal-transducing co-receptor for the Nogo receptor (NgR) in MAG-mediated axon repulsion expanded p75NTR's role beyond neurotrophin biology into myelin-associated growth inhibition.

    Evidence Co-IP of NgR–p75NTR, HEK reconstitution with Ca²⁺ imaging, Xenopus growth cone turning assay with anti-p75NTR blocking antibody

    PMID:12426574

    Open questions at the time
    • Downstream signaling intermediates between p75NTR and growth cone cytoskeleton not defined
    • Whether other TNFR family members can substitute for p75NTR in this complex unclear
  3. 2003 High

    Identifying JNK-dependent Bad phosphorylation and oligomerization as the required pro-apoptotic effector cascade downstream of p75NTR resolved a key gap in how a death-domain receptor without caspase-recruitment motifs activates the intrinsic apoptotic pathway.

    Evidence p75NTR overexpression in cortical neurons and PC12 cells; Bad dominant-negative/RNAi; cytochrome c release and caspase activation assays

    PMID:14673001

    Open questions at the time
    • Identity of the kinase directly phosphorylating Bad downstream of JNK not established
    • Relative contribution of Bad vs. other BH3-only proteins in primary neurons unknown
  4. 2004 High

    Showing that the p75NTR-interacting protein SC1 represses cyclin E transcription via HDAC1/2/3 recruitment provided a mechanism for p75NTR-associated cell cycle arrest.

    Evidence Gal4 tethering repression assay, HDAC co-IP, promoter-reporter, BrdU incorporation, TSA treatment

    PMID:15051733

    Open questions at the time
    • Whether SC1 is required for p75NTR-dependent growth arrest in vivo not tested
    • Regulation of SC1 nuclear entry by p75NTR signaling incompletely defined
  5. 2005 High

    Connecting p75NTR to amyloidogenic APP processing via NGF-dependent ceramide production from neutral sphingomyelinase revealed a non-apoptotic pathological output of p75NTR with direct relevance to age-dependent Aβ accumulation.

    Evidence p75NTR KO mice, nSMase inhibitor treatment, APP cleavage and Aβ quantification in aging brain, caloric restriction

    PMID:15966860

    Open questions at the time
    • Precise mechanism by which ceramide activates β-secretase not defined
    • Whether p75NTR directly interacts with APP at this stage was unknown
  6. 2007 High

    Two discoveries expanded p75NTR's roles beyond neurons: Rho-dependent regulation of hepatic stellate cell differentiation and Sp1-mediated transcriptional induction of p75NTR under osmotic stress established non-neuronal signaling functions and a defined transcriptional regulatory mechanism.

    Evidence p75NTR KO mice with in vivo liver injury plus Rho inhibition (hepatic stellate cells); ChIP, Sp1 siRNA, promoter-reporter assays (osmotic stress)

    PMID:17287525 PMID:17395831

    Open questions at the time
    • Specific Rho effectors mediating HSC differentiation downstream of p75NTR not identified
    • Whether Sp1-mediated induction operates in all cell types expressing p75NTR unknown
  7. 2008 High

    Genetic demonstration that the adaptor NRAGE is required for p75NTR-dependent developmental apoptosis of sympathetic neurons and JNK activation identified the proximal intracellular mediator linking the receptor to its death cascade in vivo.

    Evidence NRAGE KO mice phenocopying p75NTR KO in sympathetic neuron survival and catagen hair follicle defects; BDNF-dependent JNK assay

    PMID:18772898

    Open questions at the time
    • How NRAGE physically bridges p75NTR to JNK kinases not structurally resolved
    • Whether NRAGE mediates all p75NTR apoptotic contexts or only developmental ones unknown
  8. 2009 High

    Structural and trafficking studies revealed that proNGF binds p75NTR in a symmetric 2:2 mode (distinct from mature NGF) forming a ternary complex with sortilin, and that cPKC phosphorylation of Ser266 acts as an endosomal sorting signal to prolong p75NTR death signaling — together explaining how ligand identity and post-translational modification determine signaling duration and outcome.

    Evidence X-ray crystallography of proNGF–p75NTR at 3.75 Å with SPR (structure); Ser266 mutagenesis, mass spectrometry, retrograde transport tracing (trafficking)

    PMID:19710323 PMID:20036257

    Open questions at the time
    • How the 2:2 proNGF complex structurally accommodates sortilin unresolved
    • Structural basis for the distinct signaling outputs of symmetric vs. asymmetric complexes unknown
  9. 2015 High

    Multiple discoveries in 2015 established that p75NTR exists predominantly as monomers (with some trimers), that NGF-driven redistribution into cholesterol-rich domains—not oligomerization per se—is required for pro-neurotrophin apoptosis signaling, and that proBDNF–p75NTR suppresses neuronal excitability via a Rac1–PI4K–PIP2 pathway modulating TRPC channels.

    Evidence Single-molecule imaging, oligomerization/fractionation assays, growth cone retraction assays (oligomeric state); p75NTR conditional KO mice, electrophysiology, Rac1/PI4K inhibitors (excitability); NMR in nanodiscs (domain dynamics); PKA-Ser303 mutagenesis, PDLIM1 pulldown, in vivo glioma xenograft (invasion)

    PMID:26119933 PMID:26134656 PMID:26287629 PMID:26311773 PMID:31515449

    Open questions at the time
    • How cholesterol-domain partitioning mechanistically switches signaling output remains unclear
    • Whether the Rac1–PI4K–PIP2 pathway operates outside entorhinal cortex untested
    • Structural mechanism by which the disordered chopper domain transmits signal across the membrane unknown
  10. 2018 High

    Showing that proNGF–p75NTR drives tau hyperphosphorylation through AKT/GSK3β inactivation, rescuable by soluble p75NTR ectodomain in P301L mice, connected p75NTR to tauopathy and identified a potential therapeutic target.

    Evidence P301L tau transgenic mice with p75NTR genetic reduction or p75ECD-Fc treatment, AKT/GSK3β phosphorylation, behavioral memory testing

    PMID:29867188

    Open questions at the time
    • Whether p75NTR-dependent tau phosphorylation is cell-autonomous or involves glial intermediates not resolved
    • Mechanism by which p75NTR activates AKT vs. suppresses it in other contexts not reconciled
  11. 2020 High

    Three studies in 2020 broadened p75NTR function: direct interaction with APP at the plasma membrane regulates APP trafficking and amyloidogenic processing; PI3K/Akt/β-catenin mediates p75NTR-driven osteogenic differentiation; and NGFR-high melanoma cells induce BDNF to resist T cell killing.

    Evidence p75NTR knock-in mice crossed to 5xFAD with APP co-IP and trafficking assays; p75NTR KO mice with micro-CT and PI3K pharmacological epistasis in ectomesenchymal stem cells; chronic T cell co-culture with melanoma, NGFR pharmacological inhibition, xenograft

    PMID:32215984 PMID:32770055 PMID:33258176

    Open questions at the time
    • Structural basis of p75NTR–APP interaction unknown
    • Whether PI3K/Akt/β-catenin pathway for osteogenesis applies to other mesenchymal lineages untested
    • Mechanism linking NGFR to BDNF induction in melanoma not biochemically defined
  12. 2021 High

    NGFR on melanoma-derived small extracellular vesicles activates ERK/NF-κB/ICAM-1 signaling in lymphatic endothelial cells to drive lymphangiogenesis and metastasis, while proBDNF–p75NTR–JNK/NF-κB mediates denervation-induced muscle inflammation, revealing cell-non-autonomous and non-neuronal inflammatory roles.

    Evidence sEV transfer to lymphatic endothelial cells with NGFR ablation and in vivo metastasis model; sciatic denervation with LM11A-31 inhibitor and muscle-specific BDNF KO

    PMID:34678261 PMID:34957415

    Open questions at the time
    • Ligand activating NGFR on sEVs in the lymphatic niche not identified
    • Whether p75NTR inhibition can reverse established denervation atrophy unknown
  13. 2023 High

    NGFR promotes neurogenesis by suppressing reactive astrocyte Lcn2/Slc22a17 signaling and drives NK cell immune evasion in melanoma via SCD-mediated lipid remodeling, further diversifying its functional repertoire.

    Evidence Hippocampal NGFR overexpression in APP/PS1dE9 mice with single-cell transcriptomics and Slc22a17 knockdown; NK cell cytotoxicity assays with SCD siRNA/pharmacological inhibition and in vivo adoptive transfer

    PMID:36638181 PMID:37429840

    Open questions at the time
    • Mechanism by which NGFR represses Lcn2 transcription not defined
    • Whether SCD upregulation is transcriptionally driven by NGFR or indirect unknown
    • Integration of neurogenic and amyloid-reducing effects of NGFR overexpression mechanistically unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major unresolved questions include the structural mechanism by which ligand binding and cholesterol-domain partitioning switch p75NTR between pro-survival and pro-apoptotic states, how the disordered juxtamembrane domain transmits signal across the membrane, and how the same receptor drives opposing outcomes (e.g., PI3K/Akt activation for osteogenesis vs. PTEN-mediated Akt suppression for apoptosis) in different cellular contexts.
  • No full-length p75NTR signaling complex structure available
  • Context-dependent switching mechanism between survival and death signaling not resolved
  • Relative contributions of ICD cleavage vs. intact receptor signaling in most biological contexts unclear

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0098772 molecular function regulator activity 4 GO:0060090 molecular adaptor activity 3
Localization
GO:0005886 plasma membrane 6 GO:0005768 endosome 2 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-5357801 Programmed Cell Death 4 R-HSA-168256 Immune System 3 R-HSA-1266738 Developmental Biology 2
Partners
ITGA9MAGED1NTRK1NTRK2NTRK3PDLIM1RTN4RSORT1
Complex memberships
p75NTR–NgRp75NTR–TrkA/B/CproNGF–sortilin–p75NTR

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 p75NTR (NGFR) acts as a co-receptor with the Nogo-66 receptor (NgR) for myelin-associated glycoprotein (MAG) signaling. Co-immunoprecipitation showed NgR–p75NTR association; p75NTR was required for MAG-induced intracellular Ca2+ elevation in HEK cells expressing NgR, and an anti-p75NTR antibody abolished MAG-induced repulsive axonal growth cone turning in Xenopus neurons. Co-immunoprecipitation, HEK cell reconstitution, Xenopus growth cone turning assay, Ca2+ imaging Nature neuroscience High 12426574
1999 p75NTR physically associates with TrkA, TrkB, and TrkC (but not EGFR) via both extracellular and intracellular domains, as shown by co-precipitation in co-transfected cells. Blocking TrkB autophosphorylation reduced the intracellular but not extracellular domain-mediated interaction. Co-expression of p75NTR with TrkB increased specificity of TrkB activation by BDNF over NT-3 and NT-4/5. Co-immunoprecipitation with deletion constructs, autophosphorylation blockade, ligand-specificity assay in transfected cells The EMBO journal High 9927421
2003 p75NTR overexpression activates JNK, which phosphorylates and oligomerizes the BH3-only protein Bad, leading to cytochrome c release and activation of caspases 9, 6, and 3. Bad dominant-negatives or Bad RNAi abolished p75NTR-induced apoptosis, establishing Bad phosphorylation downstream of p75NTR–JNK as a required step in the apoptotic cascade. p75NTR overexpression in primary cortical neurons and PC12/glioma cells, caspase activation assays, cytochrome c fractionation, Bad dominant-negative and RNAi loss-of-function The Journal of neuroscience High 14673001
2007 p75NTR signals through the small GTPase Rho to regulate hepatic stellate cell (HSC) differentiation to myofibroblasts. p75NTR-null HSCs failed to differentiate and did not support hepatocyte proliferation; inhibition of p75NTR signaling to Rho impaired HSC differentiation, and p75NTR depletion in vivo exacerbated liver pathology. p75NTR knockout mice, in vivo liver injury model, primary HSC culture, Rho signaling inhibition Science High 17395831
2005 p75NTR activates amyloid precursor protein (APP) β-cleavage and Aβ generation via NGF-dependent ceramide production (neutral sphingomyelinase pathway), while TrkA reduces β-cleavage. Normal aging switches neurons from TrkA to p75NTR signaling, increasing Aβ; this is abolished in p75NTR knockout mice and blocked by nSMase inhibitors or caloric restriction. p75NTR knockout mice, nSMase inhibitor treatment, caloric restriction, APP processing/Aβ quantification in aging brain The Biochemical journal High 15966860
2009 Crystal structure of proNGF complexed with p75NTR at 3.75-Å resolution reveals a 2:2 symmetric binding mode (distinct from the asymmetric mature NGF–p75NTR complex). The pro regions are disordered and loop 2 of the NGF dimer undergoes conformational changes. Surface plasmon resonance and cell-based assays show calcium ions promote a stable ternary proNGF–sortilin–p75NTR complex. X-ray crystallography, surface plasmon resonance, cell-based binding assays Journal of molecular biology High 20036257
2010 p75NTR-activated proNGF induces PTEN expression in rat CNS neurons, which suppresses TrkB/PI3K/Akt survival signaling and shifts the balance toward apoptosis. Inhibition or knockdown of PTEN restored Akt phosphorylation and protected neurons from proNGF-induced death both in vitro and in vivo after pilocarpine-induced seizures. Primary basal forebrain neuron culture, PI3K/Akt phosphorylation assays, PTEN knockdown/inhibition, in vivo pilocarpine model The Journal of neuroscience High 21084616
2004 The p75NTR-interacting protein SC1 acts as a transcriptional repressor of cyclin E through recruitment of HDACs 1, 2, and 3, requiring SC1's PR domain and zinc finger domains. SC1 represses the cyclin E promoter, providing a mechanism for p75NTR-associated growth arrest. Gal4 tethering transcriptional repression assay, HDAC co-immunoprecipitation, promoter-reporter assays, BrdU incorporation, trichostatin A treatment The Journal of cell biology High 15051733
2015 p75NTR glioma invasion requires PKA-dependent phosphorylation of Ser303, which generates a phosphorylated PDZ-binding motif (SPV) at the C-terminus that recruits the adaptor PDLIM1. Deletion or mutation of the PDZ motif or shRNA knockdown of PDLIM1 abolished p75NTR-mediated glioma invasion in vitro and in vivo. PKA pharmacological inhibition, S303G and ΔSPV/SPM mutants, peptide-based pulldown identifying PDLIM1, shRNA knockdown in glioma stem cells and xenograft model Oncogene High 26119933
2015 NMR spectroscopy of the p75NTR transmembrane and intracellular domains in lipid-protein nanodiscs reveals high flexibility and disorder in the juxtamembrane 'chopper' domain, uncoupling death domain motion from transmembrane helix motion. No intracellular domain showed propensity to interact with the membrane or self-associate, informing the receptor activation mechanism. Solution NMR spectroscopy in lipid-protein nanodiscs of varying size and composition Biophysical journal High 26287629
2015 p75NTR predominantly assembles as a trimer at the cell surface, with monomers also present. Trimers are not required for ligand-independent or ligand-dependent growth cone retraction; however, monomers can induce acute morphological effects in neurons. NGF stimulation shifts wild-type p75NTR into cholesterol-rich membrane regions (unlike an oligomerization-deficient mutant), and this partitioning is linked to proNT-induced apoptosis signaling. Biochemical oligomerization assays, brain tissue fractionation, growth cone retraction functional assay, cholesterol-rich domain fractionation, single-molecule imaging The Journal of neuroscience High 26311773 31515449
2019 Single-molecule live-cell imaging shows that the vast majority of p75NTR receptors are monomers before and after neurotrophin activation. NGF stimulation shifts wild-type p75NTR into cholesterol-rich membrane domains, enabling proNT-induced apoptosis; a receptor mutant lacking putative oligomerization residues fails this shift and cannot mediate proNT apoptosis. Surface accumulation of p75NTR (rather than oligomerization) drives growth cone collapse. Single-molecule tracking in living cells, cholesterol-domain fractionation, apoptosis and growth cone retraction assays with wild-type vs. mutant p75NTR PNAS High 31515449
2014 Rabies virus (RABV) glycoprotein binds p75NTR and is co-internalized and co-transported retrogradely in p75NTR-positive acidic compartments along axons. p75NTR-dependent RABV transport is faster and more directional (higher instantaneous velocities, fewer/shorter stops) than p75NTR-independent transport, indicating that RABV hijacks and accelerates the p75NTR retrograde axonal transport machinery. Live-cell imaging of fluorescently labeled RABV and NGF in axons, compartment co-localization, velocity analysis with and without p75NTR PLoS pathogens High 25165859
2009 Phosphorylation of p75NTR on Ser266 by conventional protein kinase C (cPKC) acts as a sorting signal that delays accumulation of p75NTR-bound NGF in multivesicular bodies and lysosomes compared with trk-bound neurotrophins, thereby prolonging p75NTR death signaling. This was shown by kinase inhibitors, mutagenesis of Ser266, and mass spectrometry identification of the phosphorylation site. Retrograde transport tracing with radiolabeled neurotrophins, ultrastructural analysis, kinase inhibitors (K252a, Gö6976), Ser266 mutagenesis, mass spectrometry The Journal of neuroscience High 19710323
2007 Hypo-osmolar stress induces p75NTR expression in primary neurons via Sp1 transcription factor. Comparative genomics identified an Sp1-rich proximal promoter element; Sp1 DNA-binding activity increased under hypo-osmolarity, Sp1 binding to the endogenous p75NTR promoter was enhanced, and Sp1 was required for hypo-osmolarity-induced p75NTR upregulation. The mechanism involves stress-induced inhibition of Sp1 protein turnover. Comparative genomics, ChIP, Sp1 siRNA knockdown, promoter-reporter assays, Sp1 turnover measurements The Journal of neuroscience High 17287525
2008 The p75NTR adaptor protein NRAGE (Maged1) is required in vivo for developmental apoptosis of sympathetic neurons. NRAGE knockout mice phenocopy p75NTR knockout mice in defective sympathetic neuron apoptosis; NRAGE-deficient neurons are resistant to BDNF-induced p75NTR-dependent apoptosis and show attenuated BDNF-dependent JNK activation. NRAGE and p75NTR are co-expressed in hair follicles and both KOs show identical catagen defects. NRAGE knockout mouse generation, primary sympathetic neuron culture, JNK activation assay, hair follicle catagen analysis, genetic epistasis Cell death and differentiation High 18772898
2008 After facial nerve axotomy, p75NTR and sortilin expression increase in Schwann cells; proNGF treatment of cultured Schwann cells increased apoptosis and p75NTR expression, indicating that the proNGF–p75NTR–sortilin axis mediates Schwann cell death after nerve injury. Immunofluorescence quantification in vivo post-axotomy, Western blot in vitro, TUNEL apoptosis assay after proNGF treatment The Laryngoscope Medium 18090258
2015 proBDNF activates p75NTR to suppress persistent firing of entorhinal cortex layer V pyramidal neurons via a Rac1–PI4K pathway that modulates PIP2 levels and PIP2-sensitive TRPC channels. Genetic deletion of p75NTR in neurons or adult mice enhances pyramidal excitability and persistent firing; function-blocking proBDNF or p75NTR antibodies also enhance firing, establishing the proBDNF–p75NTR–Rac1–PI4K–PIP2 cascade as a brake on working memory network activity. Electrophysiological recordings in brain slices, p75NTR conditional and adult knockout mice, function-blocking antibodies, Rac1 and PI4K pharmacological inhibition, calcium imaging The Journal of neuroscience High 26134656
2018 The proNGF/p75NTR pathway induces tau hyperphosphorylation via the AKT/GSK3β pathway. In P301L tau transgenic mice, genetic reduction of p75NTR or treatment with soluble p75NTR extracellular domain (p75ECD-Fc) rescued memory deficits, reduced tau phosphorylation, and restored AKT/GSK3β activity. P301L transgenic mouse model, p75NTR genetic reduction, p75ECD-Fc treatment, AKT/GSK3β phosphorylation assays, behavioral memory testing Molecular psychiatry High 29867188
2020 p75NTR interacts with APP at the plasma membrane and regulates APP internalization and intracellular trafficking in hippocampal neurons. Signaling-deficient p75NTR knock-in variants (lacking death domain or Cys259) internalize more slowly, remain in the recycling pathway, reduce APP co-localization with BACE1, and shift APP processing toward non-amyloidogenic cleavage, thereby reducing Aβ generation and AD neuropathology in 5xFAD mice. p75NTR knock-in mice (death domain deletion, Cys259 mutation), Co-IP of p75NTR with APP, APP internalization assays, BACE1 co-localization, Aβ quantification, synaptic plasticity and memory behavioral testing in 5xFAD background The EMBO journal High 33258176
2020 NGFRhi melanoma cells induce the neurotrophic factor BDNF, which contributes to T cell resistance. NGFR itself also directly confers resistance. Pharmacologic NGFR inhibition restores tumor sensitivity to T cell attack in vitro and in xenograft models. Chronic T cell exposure to patient-derived melanoma lines, BDNF functional assays, pharmacological NGFR inhibition, in vivo xenograft cytotoxicity Nature communications Medium 32770055
2021 NGFR-enriched melanoma small extracellular vesicles (sEVs) are taken up by lymphatic endothelial cells and activate ERK kinase, NF-κB, and ICAM-1 expression, promoting lymphangiogenesis and lymph node metastasis. Ablation or inhibition of NGFR in sEVs reversed the lymphangiogenic phenotype and decreased lymph node metastasis. sEV isolation and transfer to lymphatic endothelial cells, ERK/NF-κB/ICAM-1 signaling assays, NGFR ablation/inhibition in EVs, in vivo murine metastasis models Nature cancer High 34957415
2017 p75NTR/CD271 regulates melanoma phenotype switching through two mechanisms: (1) the cleaved intracellular domain of CD271 controls proliferation, and (2) CD271 interaction with TrkA modulates cell adhesiveness through dynamic regulation of cholesterol synthesis genes. CD271 overexpression/knockdown in melanoma cells, intracellular domain cleavage analysis, cholesterol synthesis gene expression profiling, cell adhesion assays, TrkA interaction studies Nature communications Medium 29215016
2023 NGFR-induced expression in the hippocampus reduces reactive astrocyte marker Lipocalin-2 (Lcn2), which otherwise suppresses neurogenesis. NGFR suppresses Lcn2/Slc22a17 signaling to promote pro-neurogenic astroglial fate; blockage of Slc22a17 recapitulated NGFR's pro-neurogenic effect. Long-term NGFR expression reduced amyloid plaques and Tau phosphorylation in APP/PS1dE9 mice. Hippocampal Ngfr overexpression (APP/PS1dE9 mice), single-cell transcriptomics, spatial proteomics, Lcn2/Slc22a17 functional knockdown, histological neurogenesis quantification, plaque/Tau assays NPJ Regenerative medicine High 37429840
2015 p75NTR forms a cation-independent complex with the α9 integrin subunit (but not other integrin subunits) on the cell membrane. The α9/p75NTR complex increases NGF-dependent cell adhesion, proliferation, and migration, and elevates MAPK Erk1/2 activation. FRET analysis indicated that cytoplasmic domains of p75NTR and α9 are not in close proximity, likely due to molecular interference by paxillin. Selective co-immunoprecipitation of α9 integrin with p75NTR in transfected glioma cells, FRET analysis, cell adhesion/proliferation/migration assays, Erk1/2 phosphorylation assay Cellular signalling Medium 25748048
2023 NGFR promotes NK cell immune evasion in melanoma by down-regulating NK cell activating ligands and up-regulating stearoyl-CoA desaturase (SCD), a lipid-remodeling enzyme. Pharmacological or siRNA-mediated inhibition of SCD reversed NGFR-induced NK cell evasion in vitro and in vivo in a mouse model with adoptively transferred human NK cells. In vitro NK cell cytotoxicity assays, in vivo mouse model with adoptive NK cell transfer, SCD siRNA knockdown and pharmacological inhibition, activating ligand expression profiling Science advances High 36638181
2016 In oral squamous cell carcinoma (OSCC), NGF stimulation of NGFR+ cells increases ESM1 (endocan) expression. ESM1 overexpression enhanced migration, invasion, and metastasis; shRNA knockdown of ESM1 in NGFR-overexpressing OSCC cells abrogated these properties and reduced tumor growth, establishing ESM1 as a downstream effector of NGFR-mediated invasion. NGF stimulation of NGFR+ murine OSCC cells, gene expression array, ESM1 overexpression and shRNA knockdown, in vitro migration/invasion assays, in vivo metastasis model Oncotarget Medium 27683113
2016 CD271 depletion in hypopharyngeal cancer cells suppressed ERK phosphorylation and induced G0 cell-cycle arrest with strong upregulation of CDKN1C (p57Kip2). Double knockdown of CD271 and CDKN1C partially rescued G0 arrest. Inhibition of CD271-RhoA signaling by TAT-Pep5 diminished in vitro migration, placing RhoA downstream of CD271 in the motility pathway. siRNA knockdown of CD271 in HPC cell lines, ERK phosphorylation assay, cell cycle analysis, CDKN1C expression analysis, double knockdown, TAT-Pep5 RhoA inhibition, migration assay, in vivo xenograft Scientific reports High 27469492
2021 In denervated skeletal muscle, pro-BDNF and p75NTR are upregulated, activating JNK and NF-κB signaling, leading to muscle atrophy and inflammation. Pharmacological inhibition of p75NTR (LM11A-31) reduced JNK activation and inflammatory cytokines; skeletal muscle-specific BDNF knockout reduced pro-BDNF, JNK activation, and inflammation, establishing the pro-BDNF–p75NTR–JNK/NF-κB axis in denervation-induced muscle inflammation. Murine sciatic denervation model, p75NTR inhibitor treatment, skeletal muscle-specific BDNF knockout, Western blot for JNK/NF-κB phosphorylation, cytokine measurement Life sciences High 34678261
2017 p75NTR on plasmacytoid dendritic cells (pDCs) modulates immune function via TLR9 activation and differential phosphorylation of IRF3 and IRF7. p75NTR modulation on pDCs influences asthma disease progression in an ovalbumin mouse model; NGF-dependent p75NTR activation on pDCs from asthma patients increased allergen-specific T cell proliferation and cytokine secretion. p75NTR expression on pDCs, TLR9 activation assays, IRF3/IRF7 phosphorylation, ovalbumin asthma mouse model, NGF stimulation of patient-derived pDCs, T cell proliferation assay Frontiers in immunology Medium 28861085
2006 Gene delivery via p75NTR-mediated retrograde axonal transport using an anti-p75NTR antibody (MC192)–poly-L-lysine complex carrying the GDNF gene demonstrated that the complex is internalized upon p75NTR binding and transported retrogradely to motor neuron cell bodies, bypassing the blood-brain barrier. GDNF expression rescued 38% of injured newborn motor neurons (vs. <12% in controls) and nearly completely reversed axotomy-induced adult motor neuron death. MC192-poly-L-lysine/pGDNF complex injection, retrograde transport tracking, GDNF transgene detection in spinal cord/brainstem, motor neuron survival quantification after sciatic or hypoglossal axotomy Experimental neurology Medium 16842780
2020 p75NTR knockout mice show reduced alveolar bone mass. In p75NTR-null ectomesenchymal stem cells (EMSCs), osteogenic differentiation capacity and PI3K/Akt/β-catenin signaling are downregulated. The PI3K inhibitor LY294002 attenuated the promotive effect of p75NTR overexpression on osteogenesis; the PI3K agonist 740Y-P reversed the inhibitory effect of p75NTR knockdown, establishing PI3K/Akt/β-catenin as the downstream pathway for p75NTR-driven osteogenic differentiation. p75NTR KO mice, micro-CT, RNA-seq of EMSCs, PI3K pharmacological modulation, p75NTR lentiviral overexpression/knockdown, osteogenic differentiation assays Cell proliferation High 32215984

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Human melanoma-initiating cells express neural crest nerve growth factor receptor CD271. Nature 578 20596026
2002 A p75(NTR) and Nogo receptor complex mediates repulsive signaling by myelin-associated glycoprotein. Nature neuroscience 374 12426574
1999 Biochemical and functional interactions between the neurotrophin receptors trk and p75NTR. The EMBO journal 363 9927421
2002 The many faces of p75NTR. Current opinion in neurobiology 269 12049931
2005 p75NTR--live or let die. Current opinion in neurobiology 267 15721744
2004 p75NTR is positively promiscuous: novel partners and new insights. Neuron 262 15157416
1997 Signalling through the neurotrophin receptor p75NTR. Current opinion in neurobiology 191 9232808
2007 Regulation of hepatic stellate cell differentiation by the neurotrophin receptor p75NTR. Science (New York, N.Y.) 154 17395831
1997 p75NTR and apoptosis: Trk-dependent and Trk-independent effects. Trends in neurosciences 154 9223218
2011 EZH2 Mediates epigenetic silencing of neuroblastoma suppressor genes CASZ1, CLU, RUNX3, and NGFR. Cancer research 153 22068036
2021 Melanoma-derived small extracellular vesicles induce lymphangiogenesis and metastasis through an NGFR-dependent mechanism. Nature cancer 145 34957415
2010 CD271 antigen defines a subset of multipotent stromal cells with immunosuppressive and lymphohematopoietic engraftment-promoting properties. Haematologica 136 20179086
2003 Apoptosis induced by p75NTR overexpression requires Jun kinase-dependent phosphorylation of Bad. The Journal of neuroscience : the official journal of the Society for Neuroscience 135 14673001
2005 A TrkA-to-p75NTR molecular switch activates amyloid beta-peptide generation during aging. The Biochemical journal 121 15966860
2007 A cell-biological model of p75NTR signaling. Journal of neurochemistry 95 17437539
2007 Nerve growth factor and tissue repair remodeling: trkA(NGFR) and p75(NTR), two receptors one fate. Cytokine & growth factor reviews 94 17531524
2009 Molecular and structural insight into proNGF engagement of p75NTR and sortilin. Journal of molecular biology 88 20036257
2010 ProNGF induces PTEN via p75NTR to suppress Trk-mediated survival signaling in brain neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 86 21084616
2020 Reversal of pre-existing NGFR-driven tumor and immune therapy resistance. Nature communications 85 32770055
2010 Anti-L-NGFR and -CD34 monoclonal antibodies identify multipotent mesenchymal stem cells in human adipose tissue. Stem cells and development 85 19929314
2008 The function of p75NTR in glia. Trends in neurosciences 82 18199491
2023 Targeted Delivery of RGD-CD146+CD271+ Human Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes Promotes Blood-Spinal Cord Barrier Repair after Spinal Cord Injury. ACS nano 79 37695238
2014 Rabies Virus Hijacks and accelerates the p75NTR retrograde axonal transport machinery. PLoS pathogens 79 25165859
2014 The nerve growth factor receptor CD271 is crucial to maintain tumorigenicity and stem-like properties of melanoma cells. PloS one 76 24799129
2002 Dual role for p75(NTR) signaling in survival and cell death: can intracellular mediators provide an explanation? Journal of neuroscience research 75 11992464
2002 Increased p75(NTR) expression in hippocampal neurons containing hyperphosphorylated tau in Alzheimer patients. Experimental neurology 73 12460612
2003 Ten years on: mediation of cell death by the common neurotrophin receptor p75(NTR). Cytokine & growth factor reviews 71 12787561
2017 low neurotrophin receptor CD271 regulates phenotype switching in melanoma. Nature communications 69 29215016
2008 Human ProNGF: biological effects and binding profiles at TrkA, P75NTR and sortilin. Journal of neurochemistry 68 18808449
2015 Potential Effect of CD271 on Human Mesenchymal Stromal Cell Proliferation and Differentiation. International journal of molecular sciences 66 26184166
1998 NGF induces apoptosis in a human neuroblastoma cell line expressing the neurotrophin receptor p75NTR. Journal of neuroscience research 61 9822157
2008 NRAGE, a p75NTR adaptor protein, is required for developmental apoptosis in vivo. Cell death and differentiation 59 18772898
2016 p75NTR and Its Ligand ProNGF Activate Paracrine Mechanisms Etiological to the Vascular, Inflammatory, and Neurodegenerative Pathologies of Diabetic Retinopathy. The Journal of neuroscience : the official journal of the Society for Neuroscience 58 27559166
2013 CD271 defines a stem cell-like population in hypopharyngeal cancer. PloS one 58 23626764
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2007 Hypo-osmolar stress induces p75NTR expression by activating Sp1-dependent transcription. The Journal of neuroscience : the official journal of the Society for Neuroscience 53 17287525
2004 The p75NTR-interacting protein SC1 inhibits cell cycle progression by transcriptional repression of cyclin E. The Journal of cell biology 53 15051733
2012 Hippocampal membrane-associated p75NTR levels are increased in Alzheimer's disease. Journal of Alzheimer's disease : JAD 52 22451321
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2019 Fast-diffusing p75NTR monomers support apoptosis and growth cone collapse by neurotrophin ligands. Proceedings of the National Academy of Sciences of the United States of America 45 31515449
2024 Exosomes derived from CD271+CD56+ bone marrow mesenchymal stem cell subpopoulation identified by single-cell RNA sequencing promote axon regeneration after spinal cord injury. Theranostics 42 38169566
1998 Histamine-containing mast cells and their relationship to NGFr-immunoreactive nerves in prurigo nodularis: a reappraisal. Journal of cutaneous pathology 40 9609137
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2023 The Molecular Pathway of p75 Neurotrophin Receptor (p75NTR) in Parkinson's Disease: The Way of New Inroads. Molecular neurobiology 38 37897634
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1999 Signaling of neuronal cell death by the p75NTR neurotrophin receptor. Molecular neurobiology 32 10595871
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2014 Implications of p75NTR for dentate gyrus morphology and hippocampus-related behavior revisited. Brain structure & function 31 24599786
2016 CD271 Down-Regulation Promotes Melanoma Progression and Invasion in Three-Dimensional Models and in Zebrafish. The Journal of investigative dermatology 30 27328305
2008 p75NTR and sortilin increase after facial nerve injury. The Laryngoscope 30 18090258
2006 GDNF gene delivery via the p75(NTR) receptor rescues injured motor neurons. Experimental neurology 29 16842780
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2005 TrkA and p75NTR in the ovary of adult cow and pig. Journal of anatomy 28 16011548
2003 Connecting the dots: trafficking of neurotrophins, lectins and diverse pathogens by binding to the neurotrophin receptor p75NTR. The European journal of neuroscience 28 12603257
2018 ProBDNF/p75NTR/sortilin pathway is activated in peripheral blood of patients with alcohol dependence. Translational psychiatry 27 29520063
2014 Intravenous application of CD271-selected mesenchymal stem cells during fracture healing. Journal of orthopaedic trauma 27 24378433
2008 Nogo receptor antagonizes p75NTR-dependent motor neuron death. Proceedings of the National Academy of Sciences of the United States of America 27 18182498
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2014 Epigenetic inactivation and tumor-suppressor behavior of NGFR in human colorectal cancer. Molecular cancer research : MCR 26 25244921
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2009 Low-affinity nerve growth factor receptor (P75 NGFR) as a marker of perineural invasion in malignant melanomas. Journal of cutaneous pathology 23 19615036
2018 Comparative characterization of CD271+ and CD271- subpopulations of CD34+ human adipose-derived stromal cells. Journal of cellular biochemistry 22 29125884
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2009 Fates of neurotrophins after retrograde axonal transport: phosphorylation of p75NTR is a sorting signal for delayed degradation. The Journal of neuroscience : the official journal of the Society for Neuroscience 19 19710323
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2013 Adipogenic and osteogenic differentiation of Lin(-)CD271(+)Sca-1(+) adipose-derived stem cells. Molecular and cellular biochemistry 18 23430356
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2005 Heparanase, TrkC and p75NTR: their functional involvement in human medulloblastoma cell invasion. International journal of oncology 17 16077909
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