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    Topic review

    NGF Gene

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    Submitted by: Lily Guo
    (This entry belongs to Entry Collection "MedlinePlus ")

    Definition

    nerve growth factor

    1. Introduction

    The NGF gene provides instructions for making a protein called nerve growth factor beta (NGFβ). This protein is important in the development and survival of nerve cells (neurons), especially those that transmit pain, temperature, and touch sensations (sensory neurons). The NGFβ protein functions by attaching (binding) to its receptors, which initiates signaling pathways inside the cell. The NGFβ protein can bind to two different receptors, the NTRK1 receptor or the p75NTR receptor. Both receptors are found on the surface of sensory neurons and other types of neurons. The binding of the NGFβ protein to the NTRK1 receptor signals these neurons to grow and to mature and take on specialized functions (differentiate). This binding also blocks signals that initiate the process of self-destruction (apoptosis). Additionally, NGFβ signaling through NTRK1 plays a role in pain sensation. It is less clear what binding with the p75NTR receptor signals. Studies suggest that p75NTR signaling can help sensory neurons grow and differentiate but can also trigger apoptosis.

    2. Health Conditions Related to Genetic Changes

    2.1. Hereditary sensory and autonomic neuropathy type V

    At least one mutation in the NGF gene has been reported to cause hereditary sensory and autonomic neuropathy type V (HSAN5), a condition characterized by the inability to feel pain and sense hot and cold. This mutation changes a single protein building block (amino acid) in the NGFβ protein. The amino acid arginine is replaced with the amino acid tryptophan at position 100 (written as Arg100Trp or R100W). Studies show that the mutated NGFβ protein cannot bind to the p75NTR receptor and that it alters the signaling through the NTRK1 receptor. In addition, people with HSAN5 have a reduced number of sensory neurons. However, the mechanism by which mutation of the NGF gene leads to the inability to feel pain and temperature sensations is unclear. Although the NGFβ protein is important in many types of neurons, only sensory neurons appear to be affected in people with HSAN5.

    3. Other Names for This Gene

    • beta-nerve growth factor

    • beta-nerve growth factor precursor

    • Beta-NGF

    • HSAN5

    • nerve growth factor (beta polypeptide)

    • nerve growth factor, beta subunit

    • NGF_HUMAN

    • NGFB

    The entry is from https://medlineplus.gov/genetics/gene/ngf

    References

    1. Capsoni S, Covaceuszach S, Marinelli S, Ceci M, Bernardo A, Minghetti L,Ugolini G, Pavone F, Cattaneo A. Taking pain out of NGF: a "painless" NGF mutant,linked to hereditary sensory autonomic neuropathy type V, with full neurotrophic activity. PLoS One. 2011 Feb 28;6(2):e17321. doi: 10.1371/journal.pone.0017321.
    2. Einarsdottir E, Carlsson A, Minde J, Toolanen G, Svensson O, Solders G,Holmgren G, Holmberg D, Holmberg M. A mutation in the nerve growth factor betagene (NGFB) causes loss of pain perception. Hum Mol Genet. 2004 Apr15;13(8):799-805.
    3. Kaplan DR, Miller FD. Neurotrophin signal transduction in the nervous system. Curr Opin Neurobiol. 2000 Jun;10(3):381-91. Review.
    4. Larsson E, Kuma R, Norberg A, Minde J, Holmberg M. Nerve growth factor R221Wresponsible for insensitivity to pain is defectively processed and accumulates asproNGF. Neurobiol Dis. 2009 Feb;33(2):221-8. doi: 10.1016/j.nbd.2008.10.012.
    5. Lewin GR, Mendell LM. Nerve growth factor and nociception. Trends Neurosci.1993 Sep;16(9):353-9. Review.
    6. Ritter AM, Lewin GR, Kremer NE, Mendell LM. Requirement for nerve growthfactor in the development of myelinated nociceptors in vivo. Nature. 1991 Apr11;350(6318):500-2.
    7. Verpoorten N, De Jonghe P, Timmerman V. Disease mechanisms in hereditarysensory and autonomic neuropathies. Neurobiol Dis. 2006 Feb;21(2):247-55.
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