NGF

Official Full Name

nerve growth factor

Organism

Homo sapiens

GeneID

4803

Background

This gene is a member of the NGF-beta family and encodes a secreted protein which homodimerizes and is incorporated into a larger complex. This protein has nerve growth stimulating activity and the complex is involved in the regulation of growth and the differentiation of sympathetic and certain sensory neurons. Mutations in this gene have been associated with hereditary sensory and autonomic neuropathy, type 5 (HSAN5), and dysregulation of this gene's expression is associated with allergic rhinitis. [provided by RefSeq, Jul 2008]

Synonyms

NGFB; HSAN5; Beta-NGF;

Bio Chemical Class

Growth factor

Protein Sequence

MSMLFYTLITAFLIGIQAEPHSESNVPAGHTIPQAHWTKLQHSLDTALRRARSAPAAAIAARVAGQTRNITVDPRLFKKRRLRSPRVLFSTQPPREAADTQDLDFEVGGAAPFNRTHRSKRSSSHPIFHRGEFSVCDSVSVWVGDKTTATDIKGKEVMVLGEVNINNSVFKQYFFETKCRDPNPVDSGCRGIDSKHWNSYCTTTHTFVKALTMDGKQAAWRFIRIDTACVCVLSRKAVRRA

Open

Disease

Alzheimer disease, Chronic pain, General pain disorder, Neurodegenerative disorder, Osteoarthritis, Pain

Approved Drug

Clinical Trial Drug

8 +

Discontinued Drug

1 +

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Detailed Information

Nerve growth factor (NGF) is a cytokine discovered by the Italian scientist Dr. R. Levi-Montalcini in 1952 and purified by the American scientist Dr. S. Cohen in 1960. It has the dual functions of neurotrophic nutrition and prominence growth. It can maintain and promote. Peripheral and central nerve cell growth, differentiation and maturation, and promote the regeneration of axons. NGF plays a key role in maintaining normal growth and development of the nervous system, repair, regeneration and functional reconstruction after injury.

NGF plays a role in the body mainly by binding to two types of receptors. One type of receptor is slow in binding kinetics with NGF, but has high affinity. These receptors are encoded by the trk proto-oncogene, and the product is a tyrosine protein kinase receptor, called TrkA. It is the most important type of receptor for NGF to exert its biological activity. NGF binds to TrkA and exerts the effect of cell survival and growth. Another type of receptor is fast in binding kinetics with NGF, but has a lower affinity, referred to as p75. NGF binds to it generally without appreciable cytological responses, and p75 promotes the binding of TrkA to low concentrations of NGF.

The Role of NGF in The Nervous System

NGF plays an important role in neuronal development. Numerous studies have shown that NGF can promote the differentiation and maturation of neural stem cells to different types of neurons, promote the directed extension of nerve fibers, and promote the synthesis and release of neurotransmitters. Further, NGF is also involved in the regulation of apoptosis. Therefore, the regulation of NGF involves the entire life cycle of the development of the nervous system. The NGF content, choline acetyltransferase (ChAT) activity and spatial learning ability of rats in different ages were studied. It was found that there was age-dependent between the three, NGF content decreased with age, and ChAT activity decreased. The corresponding spatial learning ability is reduced. It is speculated that NGF has a certain degree of nutritional effects on central cholinergic neurons and can be used to prevent cognitive impairment caused by degenerative diseases such as AD.

Figure 1. Transmission of pain by NGF. (Lane, N. E., et al. 2017)

NGF and Disease

NGF and its receptor are not only expressed in normal tissues, but also in various tumor tissues, such as pancreatic cancer, cervical cancer, precedent adenocarcinoma and neuroblastoma. The effect of NGF on tumor is either promoted or inhibited, and different types of tumor have different effects. NGF may promote the growth of certain tumors. In addition, NGF has an inhibitory effect on some tumors. NGF inhibits proliferation of small cell lung cancer and reverses its phenotype to make it benign. NGF can also promote the differentiation and maturation of tumor cells, and make them develop toward a benign direction in morphology, thus inhibiting tumor growth.

Elevated levels of NGF can be found in many inflammatory and autoimmune conditions, such as multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, and mastocytosis. Tuveri et al. examined the distribution of NGF in the skin of patients with systemic sclerosis and found that the distribution of NGF in the dermis was more intensive. In the acute inflammatory encephalitis and inflammatory infiltration of the brain in patients with multiple sclerosis, it is also found that the sacred factor is involved in the immune response. The study found that the expression of neurotrophic factor in the acute phase of bacterial meningitis can infiltrate some inflammatory cells in the brain, protect a large number of neurons in the cerebral cortex and hippocampus from inflammatory damage, and exert neuroprotective effects. The study of localized NGF treatment of vasculitic leg ulcers in patients with rheumatoid arthritis found that NGF can promote rapid healing of ulcers. In addition, NGF has a regulatory effect on sensory neuropathy in adults and may be associated with hyperalgesia in tissue inflammation.

References:

Lane, N. E. , & Corr, M. . (2017). Osteoarthritis in 2016: anti-ngf treatments for pain — two steps forward, one step back?. Nature Reviews Rheumatology, 13(2), 76-78.
Tuveri, M. A. , Passiu, G. , Mathieu, A. , & Aloe, L. . (2015). Nerve growth factor and mast cell distribution in the skin of patients with systemic sclerosis. Clinical & Experimental Rheumatology, 11(3), 319.
Tomlinson, R. , Li, Z. , Zhang, Q. , Goh, B. , Li, Z. , & Thorek, D. J. , et al. (2016). Ngf-trka signaling by sensory nerves coordinates the vascularization and ossification of developing endochondral bone. Cell Reports, 16(10), 2723-2735.

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