Abstract
Neurotrophins (NTs) are molecules regulating differentiation, maintenance, and functional plasticity of vertebrate nervous systems. Nerve growth factor (NGF) was the first to be identified in the neurotrophin family. The long scientific history of NTs provided not only advancement in the neuroscience field but opened new scenarios involving different body districts in physiological and pathological conditions, which include the immune, endocrine, and skeletal system, vascular districts, inflammation, etc. To date, many biological aspects of NTs have been clarified, but the new discoveries are still opening new insights on molecular and cellular mechanisms and systemic effects, also affecting the possible therapeutic application of NTs. This short review summarizes the main aspects of NGF biology and biochemistry, including the role of the NGF precursor molecule, high- and low-affinity receptors and related intracellular pathways, and target cells.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Aarão TL d S, de Sousa JR, ASC F, LFM F, JAS Q (2018) Nerve growth factor and pathogenesis of leprosy: review and update. Front Immunol 9:939
Aloe L, Calzà L (2004) NGF and related molecules in health and disease: preface. Prog Brain Res 146:1–544
Chao MV (2003) Neurotrophins and their receptors: a convergence point for many signalling pathways. Nat Rev Neurosci 4:299–309. https://doi.org/10.1038/nrn1078
Cohen S, Levi-Montalcini R, Hamburger V (1954) A nerve growth-stimulating factor isolated from SARCOM as 37 and 180. Proc Natl Acad Sci 40:1014–1018. https://doi.org/10.1073/pnas.40.10.1014
Costa RO, Perestrelo T, Almeida RD (2018) PROneurotrophins and CONSequences. Mol Neurobiol 55:2934–2951
Fahnestock M, Shekari A (2019) ProNGF and neurodegeneration in Alzheimer’s disease. Front Neurosci 13:129
Franco ML, Comaposada-Baró R, Vilar M (2020) Neurotrophins and Neurotrophin receptors. In: Hormonal signaling in biology and medicine. Elsevier, Amsterdam, pp 83–106
Gostynska N, Pannella M, Rocco ML, Giardino L, Aloe L, Calzà L (2020) The pleiotropic molecule NGF regulates the in vitro properties of fibroblasts, keratinocytes, and endothelial cells: implications for wound healing. Am J Physiol – Cell Physiol 318:C360–C371. https://doi.org/10.1152/ajpcell.00180.2019
Griffin N, Faulkner S, Jobling P, Hondermarck H (2018) Targeting neurotrophin signaling in cancer: the renaissance. Pharmacol Res 135:12–17
Hennigan A, O’Callaghan RM, Kelly ÁM (2007) Neurotrophins and their receptors: roles in plasticity, neurodegeneration and neuroprotection. Biochem Soc Trans 35(2):424–427. Portland Press
Huang EJ, Reichardt LF (2001) Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci 24:677–736. https://doi.org/10.1146/annurev.neuro.24.1.677
Ichim G, Tauszig-Delamasure S, Mehlen P (2012) Neurotrophins and cell death. Exp Cell Res 318:1221–1228
Iulita MF, Cuello AC (2014) Nerve growth factor metabolic dysfunction in Alzheimer’s disease and down syndrome. Trends Pharmacol Sci 35:338–348. https://doi.org/10.1016/j.tips.2014.04.010
Le Moan N, Houslay DM, Christian F, Houslay MD, Akassoglou K (2011) Oxygen-dependent cleavage of the p75 neurotrophin receptor triggers stabilization of HIF-1α. Mol Cell 44:476–490. https://doi.org/10.1016/j.molcel.2011.08.033
Lee R, Kermani P, Teng KK, Hempstead BL (2001) Regulation of cell survival by secreted proneurotrophins. Science (80-) 294:1945–1948. https://doi.org/10.1126/science.1065057
Levi-Montalcini R (1997) The Saga of the nerve growth factor. World Scientific, Singapore
Lu B, Pang PT, Woo NH (2005) The yin and yang of neurotrophin action. Nat Rev Neurosci 6:603–614
Matusica D, Skeldal S, Sykes AM, Palstra N, Sharma A, Coulson EJ (2013) An intracellular domain fragment of the p75 neurotrophin receptor (p75NTR) enhances tropomyosin receptor kinase a(TrkA) receptor function. J Biol Chem 288:11144–11154. https://doi.org/10.1074/jbc.M112.436469
Micera A, Lambiase A, Stampachiacchiere B, Bonini S, Bonini S, Levi-Schaffer F (2007) Nerve growth factor and tissue repair remodeling: trkANGFR and p75NTR, two receptors one fate. Cytokine Growth Factor Rev 18:245–256
Mok SA, Lund K, Campenot RB (2009) A retrograde apoptotic signal originating in NGF-deprived distal axons of rat sympathetic neurons in compartmented cultures. Cell Res 19:546–560. https://doi.org/10.1038/cr.2009.11
Nykjaer A, Lee R, Teng KK, Jansen P, Madsen P, Nielsen MS, Jacobsen C, Kliemannel M, Schwarz E, Willnow TE, Hempstead BL, Petersen CM (2004) Sortilin is essential for proNGF-induced neuronal cell death. Nature 427:843–848. https://doi.org/10.1038/nature02319
Pöyhönen S, Er S, Domanskyi A, Airavaara M (2019) Effects of neurotrophic factors in glial cells in the central nervous system: expression and properties in neurodegeneration and injury. Front Physiol 10:486
Reichardt LF (2006) Neurotrophin-regulated signalling pathways. Philos Trans R Soc B Biol Sci 361:1545–1564
Skaper SD (2012) The neurotrophin family of neurotrophic factors: an overview. Methods Mol Biol 846:1–12
Skaper SD (2017) Nerve growth factor: a neuroimmune crosstalk mediator for all seasons. Immunology 151:1–15
Skeldal S, Sykes AM, Glerup S, Matusica D, Palstra N, Autio H, Boskovic Z, Madsen P, Castrén E, Nykjaer A, Coulson EJ (2012) Mapping of the interaction site between sortilin and the p75 neurotrophin receptor reveals a regulatory role for the sortilin intracellular domain in p75 neurotrophin receptor shedding and apoptosis. J Biol Chem 287:43798–43809. https://doi.org/10.1074/jbc.M112.374710
Sofroniew MV, Howe CL, Mobley WC (2001) Nerve growth factor signaling, neuroprotection, and neural repair. Annu Rev Neurosci 24:1217–1281. https://doi.org/10.1146/annurev.neuro.24.1.1217
Teng KK, Felice S, Kim T, Hempstead BL (2010) Understanding proneurotrophin actions: recent advances and challenges. Dev Neurobiol 70:350–359
Trabjerg E, Kartberg F, Christensen S, Rand KD (2017) Conformational characterization of nerve growth factor- reveals that its regulatory pro-part domain stabilizes three loop regions in its mature part. J Biol Chem 292:16665–16676. https://doi.org/10.1074/jbc.M117.803320
Yuan W, Ibáñez CF, Lin Z (2019) Death domain of p75 neurotrophin receptor: a structural perspective on an intracellular signalling hub. Biol Rev 94:1282–1293. https://doi.org/10.1111/brv.12502
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2021 The Author(s), under exclusive license to Springer Nature Switzerland AG
About this chapter
Cite this chapter
Lorenzini, L., Baldassarro, V.A., Stanzani, A., Giardino, L. (2021). Nerve Growth Factor: The First Molecule of the Neurotrophin Family. In: Calzà, L., Aloe, L., Giardino, L. (eds) Recent Advances in NGF and Related Molecules. Advances in Experimental Medicine and Biology(), vol 1331. Springer, Cham. https://doi.org/10.1007/978-3-030-74046-7_1
Download citation
DOI: https://doi.org/10.1007/978-3-030-74046-7_1
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-74045-0
Online ISBN: 978-3-030-74046-7
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)