Nerve growth factor - Wikipedia Nerve growth factor From Wikipedia, the free encyclopedia Jump to navigation Jump to search NGF Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4ZBN, 1SG1, 1WWW, 2IFG, 4EDW, 4EDX Identifiers Aliases NGF, Beta-HSAN5, NGFB, nerve growth factor External IDs OMIM: 162030 MGI: 97321 HomoloGene: 1876 GeneCards: NGF Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1p13.2 Start 115,285,917 bp[1] End 115,338,249 bp[1] Gene location (Mouse) Chr. Chromosome 3 (mouse)[2] Band 3 F2.2|3 45.25 cM Start 102,469,919 bp[2] End 102,521,013 bp[2] RNA expression pattern More reference expression data Gene ontology Molecular function • peptidase inhibitor activity • GO:0048551 enzyme inhibitor activity • GO:0001948 protein binding • metalloendopeptidase inhibitor activity • nerve growth factor receptor binding • growth factor activity • receptor binding Cellular component • endosome • Golgi lumen • extracellular region • cytoplasmic vesicle • extracellular • cytosol • synaptic vesicle • axon • dendrite Biological process • negative regulation of neuron apoptotic process • regulation of neuron differentiation • neuron projection morphogenesis • negative regulation of peptidase activity • neurotrophin TRK receptor signaling pathway • activation of MAPKK activity • cell-cell signaling • negative regulation of apoptotic process • regulation of cysteine-type endopeptidase activity involved in apoptotic process • positive regulation of axonogenesis • positive regulation of gene expression • positive regulation of apoptotic process • nerve growth factor processing • extrinsic apoptotic signaling pathway via death domain receptors • phosphatidylinositol-mediated signaling • negative regulation of cysteine-type endopeptidase activity involved in apoptotic process • microtubule-based movement • activation of cysteine-type endopeptidase activity involved in apoptotic process • positive regulation of Ras protein signal transduction • transmembrane receptor protein tyrosine kinase signaling pathway • peripheral nervous system development • memory • negative regulation of cell proliferation • regulation of receptor activity • nerve development • nerve growth factor signaling pathway • positive regulation of DNA binding • positive regulation of neuron differentiation • positive regulation of collateral sprouting • modulation of chemical synaptic transmission Sources:Amigo / QuickGO Orthologs Species Human Mouse Entrez 4803 18049 Ensembl ENSG00000134259 ENSMUSG00000027859 UniProt P01138 P01139 RefSeq (mRNA) NM_002506 NM_001112698 NM_013609 RefSeq (protein) NP_002497 NP_001106168 NP_038637 Location (UCSC) Chr 1: 115.29 – 115.34 Mb Chr 3: 102.47 – 102.52 Mb PubMed search [3] [4] Wikidata View/Edit Human View/Edit Mouse Nerve growth factor (NGF) is a neurotrophic factor and neuropeptide primarily involved in the regulation of growth, maintenance, proliferation, and survival of certain target neurons. It is perhaps the prototypical growth factor, in that it was one of the first to be described. Since it was first isolated by Nobel Laureates Rita Levi-Montalcini and Stanley Cohen in 1956, numerous biological processes involving NGF have been identified, two of them being the survival of pancreatic beta cells and the regulation of the immune system. Contents 1 Structure 2 Function 2.1 Neuronal proliferation 2.2 Proliferation of pancreatic beta cells 2.3 Regulation of the immune system 2.4 Ovulation 2.5 Romantic love 3 Mechanism of action 3.1 Neuron survival 4 History 5 Clinical significance 6 Miscellaneous 7 Interactions 8 See also 9 References 10 External links Structure[edit] NGF is initially in a 7S, 130-kDa complex of 3 proteins - Alpha-NGF, Beta-NGF, and Gamma-NGF (2:1:2 ratio) when expressed. This form of NGF is also referred to as proNGF (NGF precursor). The gamma subunit of this complex acts as a serine protease, and cleaves the N-terminal of the beta subunit, thereby activating the protein into functional NGF. The term nerve growth factor usually refers to the 2.5S, 26-kDa beta subunit of the protein, the only component of the 7S NGF complex that is biologically active (i.e. acting as signaling molecules). Function[edit] As its name suggests, NGF is involved primarily in the growth, as well as the maintenance, proliferation, and survival of nerve cells (neurons). In fact, NGF is critical for the survival and maintenance of sympathetic and sensory neurons, as they undergo apoptosis in its absence.[5] However, several recent studies suggest that NGF is also involved in pathways besides those regulating the life cycle of neurons. Neuronal proliferation[edit] NGF can drive the expression of genes such as bcl-2 by binding to the TrkA receptor, which stimulates the proliferation and survival of the target neuron. High affinity binding between proNGF, sortilin, and p75NTR can result in either survival or programmed cell death. Study results indicate that superior cervical ganglia neurons that express both p75NTR and TrkA die when treated with proNGF,[6] while NGF treatment of these same neurons results in survival and axonal growth. Survival and PCD mechanisms are mediated through adaptor protein binding to the death domain of the p75NTR cytoplasmic tail. Survival occurs when recruited cytoplasmic adaptor proteins facilitate signal transduction through tumor necrosis factor receptor members such as TRAF6, which results in the release of nuclear factor κB (NF-κB) transcription activator.[7] NF-κB regulates nuclear gene transcription to promote cell survival. Alternatively, programmed cell death occurs when TRAF6 and neurotrophin receptor interacting factor (NRIF) are both recruited to activate c-Jun N-terminal kinase (JNK); which phosphorylates c-Jun. The activated transcription factor c-Jun regulates nuclear transcription via AP-1 to increase pro-apoptotic gene transcription.[7] Proliferation of pancreatic beta cells[edit] There is evidence that pancreatic beta cells express both the TrkA and p75NTR receptors of NGF. It has been shown that the withdrawal of NGF induces apoptosis in pancreatic beta cells, signifying that NGF may play a critical role in the maintenance and survival of pancreatic beta cells.[8] Regulation of the immune system[edit] NGF plays a critical role in the regulation of both innate and acquired immunity. In the process of inflammation, NGF is released in high concentrations by mast cells, and induces axonal outgrowth in nearby nociceptive neurons. This leads to increased pain perception in areas under inflammation. In acquired immunity, NGF is produced by the Thymus as well as CD4+ T cell clones, inducing a cascade of maturation of T cells under infection.[9] Ovulation[edit] NGF is abundant in seminal plasma. Recent studies have found that it induces ovulation in some mammals e.g. “induced” ovulators, such as llamas. Surprisingly, research showed that these induced animals will also ovulate when semen from on-schedule or “spontaneous” ovulators, such as cattle is used. Its significance in humans is unknown. It was previously dubbed ovulation-inducing factor (OIF) in semen before it was identified as beta-NGF in 2012.[10] Romantic love[edit] Studies found that the concentration of NGF in the blood plasma is significantly higher in individuals who have been in a romantic relationship with another person for less than 12 months [227 (14) pg/ml], than those who are either not in a romantic relationship [149 (12) pg/ml] or have been in one for more than 12 months [123 (10) pg/ml].[11] NGF can indirectly stimulate the expression of adrenocorticotrophic hormone (ACTH) in the hypothalamic-pituitary-adrenal axis (HPA) by increasing vasopressin secretion. ACTH binds to the MC2 receptor in the zona fasciculata of the adrenal cortex, and stimulates secretion of the stress hormone cortisol.[12] This rapid increase of cortisol in the blood plasma can induce feelings of euphoria, which may explain the initial "rush" of falling in love.[13] Studies show that ACTH can in turn stimulate NGF secretion in both the cerebral cortex and the hypothalamus. Mechanism of action[edit] NGF binds with at least two classes of receptors: the tropomyosin receptor kinase A (TrkA) and low-affinity NGF receptor (LNGFR/p75NTR). Both are associated with neurodegenerative disorders. When NGF binds to the TrkA receptor, it drives the homodimerization of the receptor, which in turn causes the autophosphorylation of the tyrosine kinase segment. This leads to the activation of PI 3-kinase, ras, and PLC signaling pathways. Alternatively, the p75NTR receptor can form a heterodimer with TrkA, which has higher affinity and specificity for NGF. Studies suggest that NGF circulates throughout the entire body via the blood plasma, and is important for the overall maintenance of homeostasis.[14] Neuron survival[edit] Binding interaction between NGF and the TrkA receptor facilitates receptor dimerization and tyrosine residue phosphorylation of the cytoplasmic tail by adjacent Trk receptors.[15] Trk receptor phosphorylation sites operate as Shc adaptor protein docking sites, which undergo phosphorylation by the TrkA receptor[7] Once the cytoplasmic adaptor protein (Shc) is phosphorylated by the receptor cytoplasmic tail, cell survival is initiated through several intracellular pathways. One major pathway leads to the activation of the serine/threonine kinase, Akt. This pathway begins with the Trk receptor complex-recruitment of a second adaptor protein called growth factor-receptor bound protein-2 (Grb2) along with a docking protein called Grb2-associated Binder-1 (GAB1).[7] Subsequently, phosphatidylinositol-3 kinase (PI3K) is activated, resulting in Akt kinase activation.[7] Study results have shown that blocking PI3K or Akt activity results in death of sympathetic neurons in culture, regardless of NGF presence.[16] However, if either kinase is constitutively active, neurons survive even without NGF.[16] A second pathway contributing to cell survival occurs through activation of the mitogen-activated protein kinase (MAPK) kinase. In this pathway, recruitment of a guanine nucleotide exchange factor by the adaptor and docking proteins leads to activation of a membrane-associated G-protein known as Ras.[7] The guanine nucleotide exchange factor mediates Ras activation through the GDP-GTP exchange process. The active Ras protein phosphorylates several proteins, along with the serine/threonine kinase, Raf.[7] Raf in turn activates the MAPK cascade to facilitate ribosomal s6 kinase (RSK) activation and transcriptional regulation.[7] Both Akt and RSK, components of the PI3K-Akt and MAPK pathways respectively, act to phosphorylate the cyclic AMP response element binding protein (CREB) transcription factor.[7] Phosphorylated CREB translocates into the nucleus and mediates increased expression of anti-apoptotic proteins,[7] thus promoting NGF-mediated cell survival. However, in the absence of NGF, the expression of pro-apoptotic proteins is increased when the activation of cell death-promoting transcription factors such as c-Jun are not suppressed by the aforementioned NGF-mediated cell survival pathways.[7] History[edit] Rita Levi-Montalcini and Stanley Cohen discovered NGF in the 1950s while faculty members at Washington University in St Louis. However, its discovery, along with the discovery of other neurotrophins, was not widely recognized until 1986, when it won the Nobel Prize in Physiology or Medicine.[17][18][19] Studies in 1971 determined the primary structure of NGF. This eventually led to the discovery of the NGF gene. NGF is abundant in seminal plasma. Recent studies have found that it induces ovulation in some mammals.[20] Nerve Growth Factors (NGF) were initially discovered due to their actions during development, but NGF are not known to be involved in the function throughout the life of the animal.[21] Clinical significance[edit] Nerve growth factor prevents or reduces neuronal degeneration in animal models of neurodegenerative diseases and these encouraging results in animals have led to several clinical trials in humans.[22] NGF promotes peripheral nerve regeneration in rats.[23] The expression of NGF is increased in inflammatory diseases where it suppresses inflammation.[24] NGF appears to promote myelin repair.[25] Hence NGF may be useful for the treatment of multiple sclerosis.[26] NGF could also be involved in various psychiatric disorders, such as dementia, depression, schizophrenia, autism, Rett syndrome, anorexia nervosa, and bulimia nervosa.[27] Dysregulation of NGF signaling has also been linked to Alzheimer's disease.[28][29][30][31][32][33] Connective tissue cells genetically engineered to synthesize and secrete NGF and implanted in patients' basal forebrains reliably pumped out NGF, which enhanced the cells’ size and their ability to sprout new neural fibers. The treatment also rescued vulnerable cells, even if they already showed the trademark signs of Alzheimer's pathology. In some patients, these beneficial effects lasted almost 10 years after the treatment. Even patients who died responded positively to the therapy. Even pathological cells with protein clumps in their cell bodies and surroundings extended their fibers toward the NGF source, maintained a healthy size and activated pro-survival signals that boosted their stress resilience. Two other patients received direct injections of modified viruses containing the NGF gene directly to their basal forebrains. This allowed the gene to express longer in the brain.[34][35] Neurotrophins, including NGF, have been shown to affect many areas of the brain, including areas that are related to Rett syndrome, bipolar disorder, and Alzheimer's disease. Stress and/or anxiety are usually a precipitating factor in these disorders and affects levels of NGF, leading to impaired cognitive functioning. This impaired cognitive functioning can be seen in patients with Schizophrenia. In treatment of schizophrenia, NGF levels are increased in patients using atypical antipsychotic medication, but not in patients using typical antipsychotic medications. Patients using atypical medications usually report improved cognitive performance compared to those using typical antipsychotics. Higher NGF levels from the atypical antipsychotic medications may underlie the reduction in negative symptoms of Schizophrenia relative to typical antipsychotics.[36] NGF has been shown to restore learning ability in rats recovering from induced alcoholism[37] Rett syndrome and autism often show similar signs early in life, such as slowing development and intellectual disability. One distinguishing factor is that low levels of NGF have been found in the cerebral spinal fluid of children with Rett syndrome compared to children with Autism who have relatively normal to high levels[38] Pharmaceutical therapies with NGF-like activity can be effective in treating Rett syndrome, including better motor and cortical functioning as well as increased social communication.[39] Impairment of neuroplasticity and altered levels of neuro-trophins are involved in bipolar disorder. NGF has been found to be decreased overall in bipolar disorder patients. More specifically, while in a manic state NGF is especially low. This leads to elevated or irritable mood with increased energy and decreased need for sleep while in a manic state. This decreased NGF may serve as a biological marker when assessing the present state of a bipolar disorder patient.[40] When bipolar disorder patients were treated with lithium, their NGF concentrations increased in the frontal cortex, limbic forebrain, hippocampus, and amygdala.[41] An increase in cortical and subcortical NGF has been found in patients with Alzheimer's disease. Alzheimer's is a neurodegenerative disease with which dysregulation of NGF signaling has also been linked, causing impaired retrograde transport of NGF to certain areas of the brain. This impairment may be caused by an atypical production or use of receptors in the brain.[42] Stimulating NGF receptors via NGF infusion has been shown to increase blood flow and verbal episodic memory. These improvements have been longer lasting than other treatments for Alzheimer's.[39] Also, NGF has been shown to play a role in a number cardiovascular diseases, such as coronary atherosclerosis, obesity, type 2 diabetes, and metabolic syndrome.[43] Reduced plasma levels of NGF and BDNF have been associated with acute coronary syndromes and metabolic syndromes.[44][45] NGF is known to have insulinotropic, angiogenic, and antioxidant properties. NGF suppresses food intake.[citation needed] NGF has also been shown to accelerate wound healing. There is evidence that it could be useful in the treatment of skin ulcers and cornea ulcers.[46] In some gynecological diseases, an elevated prostaglandin E2 is thought to stimulate production of NGF which contributes to the perception of pain and increased inflammation in endometriosis.[47] Monoclonal antibodies against NGF have been used in clinical trials to modulate pain. One of these is tanezumab, another is fulranumab. Miscellaneous[edit] Nerve growth factor may contribute to increased longevity and mental capacity.[48] Centenarian Rita Levi-Montalcini took a daily solution in the form of eye drops, and has stated that her brain is more active now than it was four decades ago.[48] In 2014, researchers at the Medical University of South Carolina showed that NGF level is elevated in people who performed a single 20-minute yoga session involving om-chanting and thirumoolar pranayama, when compared to a control group.[49] Interactions[edit] Nerve growth factor has been shown to interact with TrkA[6][50][51] and p75NTR (LNGFR).[6][50] It has recently been suggested that NGF expression may be stimulated by dehydroepiandrosterone (DHEA).[52] DHEA may also act as an agonist of both TrkA and p75NTR and activate the pathways of NGF, demonstrating neurotrophic activities similar to that of NGF.[53] Adrenocorticotrophic hormone (ACTH) can also upregulate NGF expression in the brain.[54] See also[edit] Protein targeting Nervous System VGF Nerve Growth Factor-inducible, a protein whose expression is induced by NGF Neurotrophin Neurotrophin-3 Neurotrophin-4 Nerve growth factor receptor Growth factor Brain-derived neurotrophic factor Hericium erinaceus an edible mushroom that has been shown to boost NGF Huperzine A an herb-derived alkaloid that seems to boost NGF Polygala tenuifolia a Chinese herb shown to increase NGF secretion in astrocytes Therapygenetics - showing how NGF genes predict treatment outcome to cognitive behavioural therapy References[edit] ^ a b c GRCh38: Ensembl release 89: ENSG00000134259 - Ensembl, May 2017 ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000027859 - Ensembl, May 2017 ^ "Human PubMed Reference:". 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S2CID 11078370. Retrieved September 9, 2015.CS1 maint: multiple names: authors list (link) External links[edit] Nerve+Growth+Factor at the US National Library of Medicine Medical Subject Headings (MeSH) NCBI: nerve growth factor (beta polypeptide) NGF for corneal therapeutic purposes Overview of all the structural information available in the PDB for UniProt: P01138 (Human Beta-nerve growth factor) at the PDBe-KB. Overview of all the structural information available in the PDB for UniProt: P01139 (Mouse Beta-nerve growth factor) at the PDBe-KB. v t e PDB gallery 1bet: NEW PROTEIN FOLD REVEALED BY A 2.3 ANGSTROM RESOLUTION CRYSTAL STRUCTURE OF NERVE GROWTH FACTOR 1btg: CRYSTAL STRUCTURE OF BETA NERVE GROWTH FACTOR AT 2.5 A RESOLUTION IN C2 SPACE GROUP WITH ZN IONS BOUND 1sg1: Crystal Structure of the Receptor-Ligand Complex between Nerve Growth Factor and the Common Neurotrophin Receptor p75 1www: NGF IN COMPLEX WITH DOMAIN 5 OF THE TRKA RECEPTOR 2ifg: Structure of the extracellular segment of human TRKA in complex with nerve growth factor v t e Hormones Endocrine glands Hypothalamic- pituitary Hypothalamus GnRH TRH Dopamine CRH GHRH Somatostatin (GHIH) MCH Posterior pituitary Oxytocin Vasopressin Anterior pituitary FSH LH TSH Prolactin POMC CLIP ACTH MSH Endorphins Lipotropin GH Adrenal axis Adrenal cortex Aldosterone Cortisol Cortisone DHEA DHEA-S Androstenedione Adrenal medulla Epinephrine Norepinephrine Thyroid Thyroid hormones T3 T4 Calcitonin Thyroid axis Parathyroid PTH Gonadal axis Testis Testosterone AMH Inhibin Ovary Estradiol Progesterone Activin Inhibin Relaxin GnSAF Placenta hCG HPL Estrogen Progesterone Pancreas Glucagon Insulin Amylin Somatostatin Pancreatic polypeptide Pineal gland Melatonin N,N-Dimethyltryptamine 5-Methoxy-N,N-dimethyltryptamine Other Thymus Thymosins Thymosin α1 Beta thymosins Thymopoietin Thymulin Digestive system Stomach Gastrin Ghrelin Duodenum CCK Incretins GIP GLP-1 Secretin Motilin VIP Ileum Enteroglucagon Peptide YY Liver/other Insulin-like growth factor IGF-1 IGF-2 Adipose tissue Leptin Adiponectin Resistin Skeleton Osteocalcin Kidney Renin EPO Calcitriol Prostaglandin Heart Natriuretic peptide ANP BNP v t e Cell signaling: Nervous tissue: Neurotrophic factors Neurotrophins NGF BDNF NT-3 NT-4 GDNF family GDNF Artemin Neurturin Persephin Ephrins A1 A2 A3 A4 A5 B1 B2 B3 CNTF family CNTF LIF IL-6 Other GMF IGF-1 Neuregulins 1 2 3 4 PACAP VEGF v t e Growth factors Fibroblast FGF receptor ligands: FGF1/FGF2/FGF5 FGF3/FGF4/FGF6 KGF FGF7/FGF10/FGF22 FGF8/FGF17/FGF18 FGF9/FGF16/FGF20 FGF homologous factors: FGF11(FHF3) FGF12(FHF1) FGF13(FHF2) FGF14(FHF4) hormone-like: FGF15/19 FGF15 FGF19 FGF21 FGF23 EGF-like domain TGFα EGF HB-EGF TGFβ pathway TGFβ TGFβ1 TGFβ2 TGFβ3 Insulin/IGF/ Relaxin family Insulin and Insulin-like growth factor IGF1 IGF2 Relaxin family peptide hormones INSL3 INSL4 INSL5 INSL6 Relaxin 1 2 3 Platelet-derived PDGFA PDGFB PDGFC PDGFD Vascular endothelial VEGF-A VEGF-B VEGF-C VEGF-D PGF Other Nerve Hepatocyte v t e Protein: nerve tissue protein Synuclein Alpha-synuclein Beta-synuclein Gamma-synuclein Other Agrin Chimerin Granin Chromogranin A B FMR1 Gap-43 protein GLUT3 Myelin Brain natriuretic peptide Nerve growth factor SCG5 Neurogranin Neuronal calcium sensor Neuropeptide Olfactory marker protein S100 protein Calgranulin Synapsin 1 2 3 Synaptophysin Tubulin GPM6A v t e Growth factor receptor modulators Angiopoietin Agonists: Angiopoietin 1 Angiopoietin 4 Antagonists: Angiopoietin 2 Angiopoietin 3 Kinase inhibitors: Altiratinib CE-245677 Rebastinib Antibodies: Evinacumab (against angiopoietin 3) Nesvacumab (against angiopoietin 2) CNTF Agonists: Axokine CNTF Dapiclermin EGF (ErbB) EGF (ErbB1/HER1) Agonists: Amphiregulin Betacellulin EGF (urogastrone) Epigen Epiregulin Heparin-binding EGF-like growth factor (HB-EGF) Murodermin Nepidermin Transforming growth factor alpha (TGFα) Kinase inhibitors: Afatinib AG-490 Agerafenib Brigatinib Canertinib Dacomitinib Erlotinib Gefitinib Grandinin Icotinib Lapatinib Neratinib Osimertinib Vandetanib WHI-P 154 Antibodies: Cetuximab Depatuxizumab Depatuxizumab mafodotin Futuximab Imgatuzumab Matuzumab Necitumumab Nimotuzumab Panitumumab Zalutumumab ErbB2/HER2 Agonists: Unknown/none Antibodies: Ertumaxomab Pertuzumab Trastuzumab Trastuzumab duocarmazine Trastuzumab emtansine Kinase inhibitors: Afatinib AG-490 Lapatinib Mubritinib Neratinib Tucatinib ErbB3/HER3 Agonists: Neuregulins (heregulins) (1, 2, 6 (neuroglycan C)) Antibodies: Duligotumab Patritumab Seribantumab ErbB4/HER4 Agonists: Betacellulin Epigen Heparin-binding EGF-like growth factor (HB-EGF) Neuregulins (heregulins) (1, 2, 3, 4, 5 (tomoregulin, TMEFF)) FGF FGFR1 Agonists: Ersofermin FGF (1, 2 (bFGF), 3, 4, 5, 6, 8, 10 (KGF2), 20) Repifermin Selpercatinib Trafermin Velafermin FGFR2 Agonists: Ersofermin FGF (1, 2 (bFGF), 3, 4, 5, 6, 7 (KGF), 8, 9, 10 (KGF2), 17, 18, 22) Palifermin Repifermin Selpercatinib Sprifermin Trafermin Antibodies: Aprutumab Aprutumab ixadotin FGFR3 Agonists: Ersofermin FGF (1, 2 (bFGF), 4, 8, 9, 18, 23) Selpercatinib Sprifermin Trafermin Antibodies: Burosumab (against FGF23) FGFR4 Agonists: Ersofermin FGF (1, 2 (bFGF), 4, 6, 8, 9, 19) Trafermin Unsorted Agonists: FGF15/19 HGF (c-Met) Agonists: Hepatocyte growth factor Potentiators: Dihexa (PNB-0408) Kinase inhibitors: Altiratinib AM7 AMG-458 Amuvatinib BMS-777607 Cabozantinib Capmatinib Crizotinib Foretinib Golvatinib INCB28060 JNJ-38877605 K252a MK-2461 PF-04217903 PF-2341066 PHA-665752 SU-11274 Tivantinib Volitinib Antibodies: Emibetuzumab Ficlatuzumab Flanvotumab Onartuzumab Rilotumumab Telisotuzumab Telisotuzumab vedotin IGF IGF-1 Agonists: des(1-3)IGF-1 Insulin-like growth factor-1 (somatomedin C) IGF-1 LR3 Insulin-like growth factor-2 (somatomedin A) Insulin Mecasermin Mecasermin rinfabate Kinase inhibitors: BMS-754807 Linsitinib NVP-ADW742 NVP-AEW541 OSl-906 Antibodies: AVE-1642 Cixutumumab Dalotuzumab Figitumumab Ganitumab Robatumumab R1507 Teprotumumab Xentuzumab (against IGF-1 and IGF-2) IGF-2 Agonists: Insulin-like growth factor-2 (somatomedin A) Antibodies: Dusigitumab Xentuzumab (against IGF-1 and IGF-2) Others Binding proteins: IGFBP (1, 2, 3, 4, 5, 6, 7) Cleavage products/derivatives with unknown target: Glypromate (GPE, (1-3)IGF-1) Trofinetide LNGF (p75NTR) Agonists: BDNF BNN-20 BNN-27 Cenegermin DHEA DHEA-S NGF NT-3 NT-4 Antagonists: ALE-0540 Dexamethasone EVT-901 (SAR-127963) Testosterone Antibodies: Against NGF: ABT-110 (PG110) ASP-6294 Fasinumab Frunevetmab Fulranumab MEDI-578 Ranevetmab Tanezumab Aptamers: Against NGF: RBM-004 Decoy receptors: LEVI-04 (p75NTR-Fc) PDGF Agonists: Becaplermin Platelet-derived growth factor (A, B, C, D) Kinase inhibitors: Agerafenib Axitinib Crenolanib Imatinib Lenvatinib Masitinib Motesanib Nintedanib Pazopanib Radotinib Quizartinib Ripretinib Sunitinib Sorafenib Toceranib Antibodies: Olaratumab Ramucirumab Tovetumab RET (GFL) GFRα1 Agonists: Glial cell line-derived neurotrophic factor (GDNF) Liatermin Kinase inhibitors: Vandetanib GFRα2 Agonists: Neurturin (NRTN) Kinase inhibitors: Vandetanib GFRα3 Agonists: Artemin (ARTN) Kinase inhibitors: Vandetanib GFRα4 Agonists: Persephin (PSPN) Kinase inhibitors: Vandetanib Unsorted Kinase inhibitors: Agerafenib SCF (c-Kit) Agonists: Ancestim Stem cell factor Kinase inhibitors: Agerafenib Axitinib Dasatinib Imatinib Masitinib Nilotinib Pazopanib Quizartinib Sorafenib Sunitinib Toceranib TGFβ See here instead. Trk TrkA Agonists: Amitriptyline BNN-20 BNN-27 Cenegermin DHEA DHEA-S Gambogic amide NGF Tavilermide Antagonists: ALE-0540 Dexamethasone FX007 Testosterone Negative allosteric modulators: VM-902A Kinase inhibitors: Altiratinib AZD-6918 CE-245677 CH-7057288 DS-6051 Entrectinib GZ-389988 K252a Larotrectinib Lestaurtinib Milciclib ONO-4474 ONO-5390556 PLX-7486 Rebastinib SNA-120 (pegylated K252a)) Antibodies: Against TrkA: GBR-900; Against NGF: ABT-110 (PG110) ASP-6294 Fasinumab Frunevetmab Fulranumab MEDI-578 Ranevetmab Tanezumab Aptamers: Against NGF: RBM-004 Decoy receptors: ReN-1820 (TrkAd5) TrkB Agonists: 3,7-DHF 3,7,8,2'-THF 4'-DMA-7,8-DHF 7,3'-DHF 7,8-DHF 7,8,2'-THF 7,8,3'-THF Amitriptyline BDNF BNN-20 Deoxygedunin Deprenyl Diosmetin DMAQ-B1 HIOC LM22A-4 N-Acetylserotonin NT-3 NT-4 Norwogonin (5,7,8-THF) R7 R13 TDP6 Antagonists: ANA-12 Cyclotraxin B Gossypetin (3,5,7,8,3',4'-HHF) Ligands: DHEA Kinase inhibitors: Altiratinib AZD-6918 CE-245677 CH-7057288 DS-6051 Entrectinib GZ-389988 K252a Larotrectinib Lestaurtinib ONO-4474 ONO-5390556 PLX-7486 TrkC Agonists: BNN-20 DHEA NT-3 Kinase inhibitors: Altiratinib AZD-6918 CE-245677 CH-7057288 DS-6051 Entrectinib GZ-389988 K252a Larotrectinib Lestaurtinib ONO-4474 ONO-5390556 PLX-7486 VEGF Agonists: Placental growth factor (PGF) Ripretinib Telbermin VEGF (A, B, C, D (FIGF)) Allosteric modulators: Cyclotraxin B Kinase inhibitors: Agerafenib Altiratinib Axitinib Cabozantinib Cediranib Lapatinib Lenvatinib Motesanib Nintedanib Pazopanib Pegaptanib Rebastinib Regorafenib Semaxanib Sorafenib Sunitinib Toceranib Tivozanib Vandetanib WHI-P 154 Antibodies: Alacizumab pegol Bevacizumab Icrucumab Ramucirumab Ranibizumab Decoy receptors: Aflibercept Others Additional growth factors: Adrenomedullin Colony-stimulating factors (see here instead) Connective tissue growth factor (CTGF) Ephrins (A1, A2, A3, A4, A5, B1, B2, B3) Erythropoietin (see here instead) Glucose-6-phosphate isomerase (GPI; PGI, PHI, AMF) Glia maturation factor (GMF) Hepatoma-derived growth factor (HDGF) Interleukins/T-cell growth factors (see here instead) Leukemia inhibitory factor (LIF) Macrophage-stimulating protein (MSP; HLP, HGFLP) Midkine (NEGF2) Migration-stimulating factor (MSF; PRG4) Oncomodulin Pituitary adenylate cyclase-activating peptide (PACAP) Pleiotrophin Renalase Thrombopoietin (see here instead) Wnt signaling proteins Additional growth factor receptor modulators: Cerebrolysin (neurotrophin mixture) See also Receptor/signaling modulators Signaling peptide/protein receptor modulators Cytokine receptor modulators Retrieved from "https://en.wikipedia.org/w/index.php?title=Nerve_growth_factor&oldid=993248899" Categories: Genes on human chromosome 1 Neurotrophic factors Peptide hormones Growth factors Developmental neuroscience Proteins Hidden categories: CS1: long volume value CS1 maint: multiple names: authors list All articles with unsourced statements Articles with unsourced statements from June 2012 Navigation menu Personal tools Not logged in Talk Contributions Create account Log in Namespaces Article Talk Variants Views Read Edit View history More Search Navigation Main page Contents Current events Random article About Wikipedia Contact us Donate Contribute Help Learn to edit Community portal Recent changes Upload file Tools What links here Related changes Upload file Special pages Permanent link Page information Cite this page Wikidata item Print/export Download as PDF Printable version In other projects Wikimedia Commons Languages العربية Català Deutsch Eesti Español Euskara فارسی Français Gaeilge Galego Bahasa Indonesia Italiano עברית Nederlands Português Русский Suomi Svenska Українська Edit links This page was last edited on 9 December 2020, at 16:23 (UTC). 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