nerve growth factor receptors


Summary: Cell surface receptors that bind NERVE GROWTH FACTOR; (NGF) and a NGF-related family of neurotrophic factors that includes neurotrophins, BRAIN-DERIVED NEUROTROPHIC FACTOR and CILIARY NEUROTROPHIC FACTOR.

Top Publications

  1. Lykissas M, Batistatou A, Charalabopoulos K, Beris A. The role of neurotrophins in axonal growth, guidance, and regeneration. Curr Neurovasc Res. 2007;4:143-51 pubmed
    ..Based on these properties, these molecules may be used as therapeutic agents for treating degenerative diseases and traumatic injuries of both the central and peripheral nervous system. ..
  2. Hallböök F, Wilson K, Thorndyke M, Olinski R. Formation and evolution of the chordate neurotrophin and Trk receptor genes. Brain Behav Evol. 2006;68:133-44 pubmed
  3. Bothwell M. Evolution of the neurotrophin signaling system in invertebrates. Brain Behav Evol. 2006;68:124-32 pubmed
    ..Remarkably, it appears that evolution of a p75(NTR) ortholog represented one of the earliest events in the expansion of the tumor necrosis factor receptor superfamily. ..
  4. Peleshok J, Saragovi H. Functional mimetics of neurotrophins and their receptors. Biochem Soc Trans. 2006;34:612-7 pubmed
    ..The end result is small molecule peptidomimetics with properties favourable over proteins. The present review will offer a general overview of these strategies with a few proven examples from our laboratory. ..
  5. Santucci L, Agostini M, Bruscoli S, Mencarelli A, Ronchetti S, Ayroldi E, et al. GITR modulates innate and adaptive mucosal immunity during the development of experimental colitis in mice. Gut. 2007;56:52-60 pubmed
    ..Therefore, targeting the GITR/GITRL system signalling may represent a potential pharmacological tool for the treatment of IBD. ..
  6. Dang C, Zhang Y, Ma Q, Shimahara Y. Expression of nerve growth factor receptors is correlated with progression and prognosis of human pancreatic cancer. J Gastroenterol Hepatol. 2006;21:850-8 pubmed
    The aim of the present study was to investigate the prognostic value of the two types of nerve growth factor receptors (NGFR), namely high-affinity receptor TrkA and low-affinity receptor p75NGFR, in pancreatic cancer...
  7. Freund Michel V, Frossard N. The nerve growth factor and its receptors in airway inflammatory diseases. Pharmacol Ther. 2008;117:52-76 pubmed
  8. Ibanez C, Ernfors P. Hierarchical control of sensory neuron development by neurotrophic factors. Neuron. 2007;54:673-5 pubmed
  9. Shevach E, Stephens G. The GITR-GITRL interaction: co-stimulation or contrasuppression of regulatory activity?. Nat Rev Immunol. 2006;6:613-8 pubmed publisher
    ..Here we propose a model in which GITR-GITR-ligand interactions co-stimulate both responder T-cell functions and the suppressive functions of T(Reg) cells. ..

More Information


  1. Ramirez Montagut T, Chow A, Hirschhorn Cymerman D, Terwey T, Kochman A, Lu S, et al. Glucocorticoid-induced TNF receptor family related gene activation overcomes tolerance/ignorance to melanoma differentiation antigens and enhances antitumor immunity. J Immunol. 2006;176:6434-42 pubmed
    ..Thus, we conclude that overall, GITR stimulation overcomes self-tolerance/ignorance and enhances T cell-mediated antitumor activity with minimal autoimmunity. ..
  2. Schindowski K, Belarbi K, Buee L. Neurotrophic factors in Alzheimer's disease: role of axonal transport. Genes Brain Behav. 2008;7 Suppl 1:43-56 pubmed publisher
  3. Zhou P, L italien L, Hodges D, Schebye X. Pivotal roles of CD4+ effector T cells in mediating agonistic anti-GITR mAb-induced-immune activation and tumor immunity in CT26 tumors. J Immunol. 2007;179:7365-75 pubmed
  4. Price R, Milne S, Sharkey J, Matsuoka N. Advances in small molecules promoting neurotrophic function. Pharmacol Ther. 2007;115:292-306 pubmed
  5. Terry A, Gearhart D, Warner S, Zhang G, Bartlett M, Middlemore M, et al. Oral haloperidol or risperidone treatment in rats: temporal effects on nerve growth factor receptors, cholinergic neurons, and memory performance. Neuroscience. 2007;146:1316-32 pubmed
    ..5 mg/kg/day) on a water maze repeated acquisition procedure, the levels of nerve growth factor receptors, and two important cholinergic proteins, the vesicular acetylcholine transporter and the high affinity ..
  6. Costantini C, Scrable H, Puglielli L. An aging pathway controls the TrkA to p75NTR receptor switch and amyloid beta-peptide generation. EMBO J. 2006;25:1997-2006 pubmed
    ..We also show that hyperactivation of IGF1-R signaling in p44 transgenic animals, which show an accelerated form of aging, is characterized by early TrkA-to-p75(NTR) switch and increased production of Abeta in the brain. ..
  7. Hougardy J, Verscheure V, Locht C, Mascart F. In vitro expansion of CD4+CD25highFOXP3+CD127low/- regulatory T cells from peripheral blood lymphocytes of healthy Mycobacterium tuberculosis-infected humans. Microbes Infect. 2007;9:1325-32 pubmed
  8. Yamamoto N, Akamatsu H, Hasegawa S, Yamada T, Nakata S, Ohkuma M, et al. Isolation of multipotent stem cells from mouse adipose tissue. J Dermatol Sci. 2007;48:43-52 pubmed
    ..The rate of differentiation into adipocytes, osteoblasts and neuronal cells was higher for p75NTR-positive cells than for p75NTR-negative cells. p75NTR proved to be a useful marker to isolate adipose tissue-derived stem cells (ASCs). ..
  9. Sugiura A, Ohtori S, Yamashita M, Inoue G, Yamauchi K, Koshi T, et al. Existence of nerve growth factor receptors, tyrosine kinase a and p75 neurotrophin receptors in intervertebral discs and on dorsal root ganglion neurons innervating intervertebral discs in rats. Spine (Phila Pa 1976). 2008;33:2047-51 pubmed publisher
    ..8% +/- 5.1%. These percentages were similar for each level. Rat L5/6 intervertebral discs were innervated by multisegmental levels of DRG. Most DRG neurons innervating the discs were positive for 2 types of NGF receptors. ..
  10. Lin B, Pirrung M, Deng L, Li Z, Liu Y, Webster N. Neuroprotection by small molecule activators of the nerve growth factor receptor. J Pharmacol Exp Ther. 2007;322:59-69 pubmed
    ..These compounds represent a new class of TrkA activators that could have potential utility in the treatment of neurodegenerative diseases. ..
  11. Capsoni S, Cattaneo A. On the molecular basis linking Nerve Growth Factor (NGF) to Alzheimer's disease. Cell Mol Neurobiol. 2006;26:619-33 pubmed
  12. Grohmann U, Volpi C, Fallarino F, Bozza S, Bianchi R, Vacca C, et al. Reverse signaling through GITR ligand enables dexamethasone to activate IDO in allergy. Nat Med. 2007;13:579-86 pubmed
    ..Induction of IDO could be an important mechanism underlying the anti-inflammatory action of corticosteroids. ..
  13. Ronchetti S, Nocentini G, Bianchini R, Krausz L, Migliorati G, Riccardi C. Glucocorticoid-induced TNFR-related protein lowers the threshold of CD28 costimulation in CD8+ T cells. J Immunol. 2007;179:5916-26 pubmed
    ..Our results indicate that GITR influences CD8(+) T cell response to CD28 costimulation, lowering the threshold of CD8(+) T cell activation. ..
  14. Pietra G, Manzini C, Vitale M, Balsamo M, Ognio E, Boitano M, et al. Natural killer cells kill human melanoma cells with characteristics of cancer stem cells. Int Immunol. 2009;21:793-801 pubmed publisher
    ..Since CSC have been reported to be both drug resistant and radioresistant, our present data suggest that NK-based adoptive immunotherapy could represent a novel therapeutic approach to possibly eradicate metastatic melanoma. ..
  15. Longo F, Yang T, KNOWLES J, Xie Y, Moore L, Massa S. Small molecule neurotrophin receptor ligands: novel strategies for targeting Alzheimer's disease mechanisms. Curr Alzheimer Res. 2007;4:503-6 pubmed
  16. Kamimura Y, Iwai H, Piao J, Hashiguchi M, Azuma M. The glucocorticoid-induced TNF receptor-related protein (GITR)-GITR ligand pathway acts as a mediator of cutaneous dendritic cell migration and promotes T cell-mediated acquired immunity. J Immunol. 2009;182:2708-16 pubmed publisher
    ..Our findings provide important implications for understanding the molecular bases of KC-LC interactions and for developing new therapeutic strategies in skin disease. ..
  17. Burgess R, Jucius T, Ackerman S. Motor axon guidance of the mammalian trochlear and phrenic nerves: dependence on the netrin receptor Unc5c and modifier loci. J Neurosci. 2006;26:5756-66 pubmed
    ..In addition, they demonstrate the importance of modifier genes in vertebrate axonal guidance. ..
  18. Zhou Z, Song X, Berezov A, Zhang G, Li Y, Zhang H, et al. Human glucocorticoid-induced TNF receptor ligand regulates its signaling activity through multiple oligomerization states. Proc Natl Acad Sci U S A. 2008;105:5465-70 pubmed publisher
    ..The studies address the functional implications and structural models for a process by which hGITRL utilizes multiple oligomerization states to regulate GITR-mediated signaling during T cell costimulation. ..
  19. Cuzzocrea S, Ronchetti S, Genovese T, Mazzon E, Agostini M, Di Paola R, et al. Genetic and pharmacological inhibition of GITR-GITRL interaction reduces chronic lung injury induced by bleomycin instillation. FASEB J. 2007;21:117-29 pubmed
    ..Our results clearly demonstrate that GITR-GITRL interaction plays an important role in the chronic lung injury induced by bleomycin in the mice. ..
  20. Mahic M, Henjum K, Yaqub S, Bjørnbeth B, Torgersen K, Tasken K, et al. Generation of highly suppressive adaptive CD8(+)CD25(+)FOXP3(+) regulatory T cells by continuous antigen stimulation. Eur J Immunol. 2008;38:640-6 pubmed publisher
    ..However, neither blocking antibodies to CTLA-4, CD80 nor CD86 could reverse CD8(+) T(R)-mediated suppression, indicating that other mechanism(s) must be employed by these cells. ..
  21. Truzzi F, Marconi A, Lotti R, Dallaglio K, French L, Hempstead B, et al. Neurotrophins and their receptors stimulate melanoma cell proliferation and migration. J Invest Dermatol. 2008;128:2031-40 pubmed publisher
    ..These results indicate that NTs, through their receptors, play a critical role in the progression of melanoma. ..
  22. Cohen A, Diab A, Perales M, Wolchok J, Rizzuto G, Merghoub T, et al. Agonist anti-GITR antibody enhances vaccine-induced CD8(+) T-cell responses and tumor immunity. Cancer Res. 2006;66:4904-12 pubmed
    ..Finally, this effect on vaccine-induced CD8(+) T-cell responses was partially independent of CD4(+) T cells (both helper and regulatory), consistent with a direct costimulatory effect on the effector CD8(+) cells themselves. ..
  23. Li L, Lao S, Wu C. Increased frequency of CD4(+)CD25(high) Treg cells inhibit BCG-specific induction of IFN-gamma by CD4(+) T cells from TB patients. Tuberculosis (Edinb). 2007;87:526-34 pubmed
  24. Grimsholm O, Guo Y, Ny T, Forsgren S. Expression patterns of neurotrophins and neurotrophin receptors in articular chondrocytes and inflammatory infiltrates in knee joint arthritis. Cells Tissues Organs. 2008;188:299-309 pubmed publisher
    ..The downregulated expression of NGF and NT receptors in articular chondrocytes in arthritis is a new aspect concerning the involvement of NTs in cartilage. ..
  25. Deppmann C, Mihalas S, Sharma N, Lonze B, Niebur E, Ginty D. A model for neuronal competition during development. Science. 2008;320:369-73 pubmed publisher
    ..We suggest that three target-initiated events are essential for rapid and robust competition between neurons: sensitization, paracrine apoptotic signaling, and protection from such effects. ..
  26. Lim A, Tan D, Price P, Kamarulzaman A, Tan H, James I, et al. Proportions of circulating T cells with a regulatory cell phenotype increase with HIV-associated immune activation and remain high on antiretroviral therapy. AIDS. 2007;21:1525-34 pubmed
    ..Proportions of circulating T cells with a regulatory cell phenotype increase with HIV-associated immune activation and remain high after 1 year on ART. ..
  27. Sáez E, Pehar M, Vargas M, Barbeito L, Maccioni R. Production of nerve growth factor by beta-amyloid-stimulated astrocytes induces p75NTR-dependent tau hyperphosphorylation in cultured hippocampal neurons. J Neurosci Res. 2006;84:1098-106 pubmed
    ..These results suggest a potential role for astrocyte-derived NGF in the progression of AD. ..
  28. Hennigan A, O Callaghan R, Kelly A. Neurotrophins and their receptors: roles in plasticity, neurodegeneration and neuroprotection. Biochem Soc Trans. 2007;35:424-7 pubmed
    ..Here, we briefly give a broad review of current knowledge of the roles of neurotrophins in the adult brain, including expression of hippocampal plasticity, neurodegeneration and exercise-induced neuroprotection. ..
  29. Patel M, Xu D, Kewin P, Choo Kang B, McSharry C, Thomson N, et al. Glucocorticoid-induced TNFR family-related protein (GITR) activation exacerbates murine asthma and collagen-induced arthritis. Eur J Immunol. 2005;35:3581-90 pubmed
    ..Our results therefore provide direct evidence that GITR can modulate both Th1- and Th2-mediated inflammatory diseases, and may be a potential target for therapeutic intervention. ..
  30. Domeniconi M, Zampieri N, Spencer T, Hilaire M, Mellado W, Chao M, et al. MAG induces regulated intramembrane proteolysis of the p75 neurotrophin receptor to inhibit neurite outgrowth. Neuron. 2005;46:849-55 pubmed
  31. Ginsberg S, Che S, Wuu J, Counts S, Mufson E. Down regulation of trk but not p75NTR gene expression in single cholinergic basal forebrain neurons mark the progression of Alzheimer's disease. J Neurochem. 2006;97:475-87 pubmed
    ..In contrast, there is a lack of regulation of p75(NTR) expression. Thus, trk defects may be a molecular marker for the transition from no cognitive impairment (NCI) to MCI, and from MCI to frank AD. ..
  32. La S, Kim E, Kwon B. In vivo ligation of glucocorticoid-induced TNF receptor enhances the T-cell immunity to herpes simplex virus type 1. Exp Mol Med. 2005;37:193-8 pubmed
    ..Our results indicate that GITR signals play a critical role in the T-cell immunity to HSV-1. ..
  33. Butowt R, von Bartheld C. Anterograde axonal transport of BDNF and NT-3 by retinal ganglion cells: roles of neurotrophin receptors. Mol Cell Neurosci. 2005;29:11-25 pubmed
    ..Thus, neither BDNF nor NT-3 utilizes p75 for anterograde transport in adult rodent RGCs, while anterograde NT-3 transport requires the p75 receptor in embryonic chicken RGCs. ..
  34. Li S, Saragovi H, Nedev H, Zhao C, Racine R, Fahnestock M. Differential actions of nerve growth factor receptors TrkA and p75NTR in a rat model of epileptogenesis. Mol Cell Neurosci. 2005;29:162-72 pubmed
  35. Dou Y, Hagströmer L, Emtestam L, Johansson O. Increased nerve growth factor and its receptors in atopic dermatitis: an immunohistochemical study. Arch Dermatol Res. 2006;298:31-7 pubmed
    ..These findings indicate that NGF and its receptors may contribute to the neurohyperplasia of AD. ..
  36. Hanabuchi S, Watanabe N, Wang Y, Wang Y, Ito T, Shaw J, et al. Human plasmacytoid predendritic cells activate NK cells through glucocorticoid-induced tumor necrosis factor receptor-ligand (GITRL). Blood. 2006;107:3617-23 pubmed
    ..This study reveals a novel function of GITR/GITRL in pDC-mediated coactivation of NK cells. ..
  37. Suvas S, Kim B, Sarangi P, Tone M, Waldmann H, Rouse B. In vivo kinetics of GITR and GITR ligand expression and their functional significance in regulating viral immunopathology. J Virol. 2005;79:11935-42 pubmed
    ..Our results are the first observations to determine in vivo kinetics of GITR and GITR-L expression after virus infection, and they emphasize the role of GITR-GITR-L interaction to regulate virus-induced immuno-inflammatory lesions. ..
  38. Cuzzocrea S, Ayroldi E, Di Paola R, Agostini M, Mazzon E, Bruscoli S, et al. Role of glucocorticoid-induced TNF receptor family gene (GITR) in collagen-induced arthritis. FASEB J. 2005;19:1253-65 pubmed
    ..In conclusion, GITR plays a critical role in the immunological response against CII and in the development of CIA. ..
  39. Esparza E, Arch R. Glucocorticoid-induced TNF receptor, a costimulatory receptor on naive and activated T cells, uses TNF receptor-associated factor 2 in a novel fashion as an inhibitor of NF-kappa B activation. J Immunol. 2005;174:7875-82 pubmed
    ..Interestingly, in contrast with its effects on signaling triggered by other TNFRs, our functional studies revealed that TRAF2 plays a novel inhibitory role in GITR-triggered NF-kappaB activation. ..
  40. Esparza E, Arch R. Glucocorticoid-induced TNF receptor functions as a costimulatory receptor that promotes survival in early phases of T cell activation. J Immunol. 2005;174:7869-74 pubmed
    ..Differences in the contributions of GITR to cell survival between naive and activated T cells suggest that the receptor triggers specific pathways depending on the activation state of the T cell. ..
  41. Teng H, Teng K, Lee R, Wright S, Tevar S, Almeida R, et al. ProBDNF induces neuronal apoptosis via activation of a receptor complex of p75NTR and sortilin. J Neurosci. 2005;25:5455-63 pubmed
    ..Together with our past findings, these data suggest that the neurotrophin family is capable of modulating diverse biological processes via differential processing of the proneurotrophins. ..
  42. Naska S, Lin D, Miller F, Kaplan D. p75NTR is an obligate signaling receptor required for cues that cause sympathetic neuron growth cone collapse. Mol Cell Neurosci. 2010;45:108-20 pubmed publisher
    ..Our data suggest that in addition to its role as a co-receptor, p75NTR may provide an obligate parallel neurotrophin-activated inhibitory pathway that broadly sensitizes neurons to inhibitory cues. ..
  43. Montcuquet N, Mercier Letondal P, Perruche S, Duperrier A, Couturier M, Bouchekioua A, et al. Regulatory T-cell expansion and function do not account for the impaired alloreactivity of ex vivo-expanded T cells. Immunology. 2008;125:320-30 pubmed publisher
    ..In conclusion, the impaired alloreactivity of T cells expanded ex vivo is not a result of preferential Treg cell expansion and/or enhanced suppressive Treg activity. ..
  44. Raap U, Deneka N, Bruder M, Kapp A, Wedi B. Differential up-regulation of neurotrophin receptors and functional activity of neurotrophins on peripheral blood eosinophils of patients with allergic rhinitis, atopic dermatitis and nonatopic subjects. Clin Exp Allergy. 2008;38:1493-8 pubmed publisher
    ..With this study, we provide new pathophysiologic insights into atopic diseases with a functional role of neurotrophins in peripheral blood eosinophils in AD and AR. ..
  45. Chu G, Yu W, Fehlings M. The p75 neurotrophin receptor is essential for neuronal cell survival and improvement of functional recovery after spinal cord injury. Neuroscience. 2007;148:668-82 pubmed
    ..We conclude that the p75(NTR) receptor is integral to neuronal cell survival and endogenous reparative mechanisms after compressive/contusive SCI. ..
  46. Schartner J, Singh A, Dahlberg P, Nettenstrom L, Seroogy C. Recurrent superantigen exposure in vivo leads to highly suppressive CD4+CD25+ and CD4+CD25- T cells with anergic and suppressive genetic signatures. Clin Exp Immunol. 2009;155:348-56 pubmed publisher
    ..These data provide a novel paradigm for chronic non-canonical T cell receptor engagement leading to highly suppressive FoxP3(+)GRAIL(+)CD4(+) T cells. ..
  47. Vecchiarelli A, Pericolini E, Gabrielli E, Agostini M, Bistoni F, Nocentini G, et al. The GITRL-GITR system alters TLR-4 expression on DC during fungal infection. Cell Immunol. 2009;257:13-22 pubmed publisher
  48. Uchida K, Nakajima H, Takamura T, Furukawa S, Kobayashi S, Yayama T, et al. Gene expression profiles of neurotrophic factors in rat cultured spinal cord cells under cyclic tensile stress. Spine (Phila Pa 1976). 2008;33:2596-604 pubmed publisher
    ..Our results suggest survival of spinal cord neuronal cells under injurious tensile stress with increased synthesis and utilization of several neurotrophic factors, receptors, and expression of proteins related to cell apoptosis. ..
  49. Scott A, Ramer M. Schwann cell p75NTR prevents spontaneous sensory reinnervation of the adult spinal cord. Brain. 2010;133:421-32 pubmed publisher
    ..The implication is that inactivating p75(NTR) in Schwann (or olfactory ensheathing) cells may enable axons to grow beyond transplants, improving the outcome of spinal cord injury. ..
  50. Fobian K, Owczarek S, Budtz C, Bock E, Berezin V, Pedersen M. Peptides derived from the solvent-exposed loops 3 and 4 of BDNF bind TrkB and p75(NTR) receptors and stimulate neurite outgrowth and survival. J Neurosci Res. 2010;88:1170-81 pubmed publisher
    ..Thus, two peptides derived from BDNF induced neurite outgrowth and enhanced neuronal survival, probably through binding to BDNF receptors. ..
  51. Boczkowski D, Lee J, Pruitt S, Nair S. Dendritic cells engineered to secrete anti-GITR antibodies are effective adjuvants to dendritic cell-based immunotherapy. Cancer Gene Ther. 2009;16:900-11 pubmed publisher
    ..To illustrate the broad utility of this strategy, we show that DC transfected with mRNA encoding GITR-ligand/Fc fusion protein is also an effective tumor vaccine adjuvant. ..
  52. Xu F, Wei Y, Lu Q, Zheng D, Zhang F, Gao E, et al. Immunohistochemical localization of sortilin and p75(NTR) in normal and ischemic rat retina. Neurosci Lett. 2009;454:81-5 pubmed publisher
  53. Levy Strumpf N, Culotti J. VAB-8, UNC-73 and MIG-2 regulate axon polarity and cell migration functions of UNC-40 in C. elegans. Nat Neurosci. 2007;10:161-8 pubmed
    ..These data are indicative of previously unidentified regulatory roles for VAB-8 and small GTPases, which act together to regulate guidance receptor functions. ..