The nerve growth factor is a neurotrophin whose main function is to ensure the proper functioning of the nervous system by maintaining and regulating neural processes, especially their growth and survival.

It is found in various parts of the body and has been linked to various functions, some of them quite surprising. If you want to know more, we invite you to continue reading this article.

What is nerve growth factor?

Nerve growth factor, better known by its acronym NGF or NGF, is a polypeptide that has been shown to be especially involved in processes such as the growth, development, maintenance and survival of nerve cells .

This substance was discovered in 1956 by Rita Levi-Montalcini and Stanley Cohen, who observed that this protein is found in the mammalian nervous system, especially involved in those cells that are involved in forming the sympathetic nervous system and the neurons involved in sensory processes.

What functions does this neurotrophin perform?

As can be assumed from its name, nerve growth factor is primarily responsible for the growth of nerve cells, but it also works to maintain them, make them proliferate and ensure their survival for as long as they are needed.

Its function becomes especially important ensuring that the cells in charge of transmitting the impulse coming from external stimuli , that is, the sensory neurons, and those of the sympathetic system can continue to live.

Below we will look more closely at some of the functions that nerve growth factor performs.

1. Neuronal proliferation

NGF causes some genes to be expressed, such as the bcl-2 gene, by coupling to the TrkA receptor (read as ‘Track’). By doing this, it stimulates the proliferation and survival of the neuron.

The binding between NGF and p75 can give rise to two antagonistic processes , as it can both induce neuron survival and programmed death. This has been seen to vary depending on the area of the nervous system.

2. Proliferation of pancreatic cells

It has been seen that beta cells in the pancreas can have TrkA and p75 receptors, which have an affinity for nerve growth factor.

It has been proven that a decrease in NGF causes these pancreatic cells to start dying , which suggests that this factor plays a very important role in their survival.

3. Regulation of the immune system

NGF promotes the regulation of immune processes, whether acquired innate or during the individual’s lifetime.

NGF is released in high doses by mast cells , which induces the growth of axons in nociceptive cells, which are in charge of detecting harmful stimuli. This increases the sensation of pain in inflamed areas.

4. Ovulation

NGF is abundantly found in semen, which has led to several studies suggesting that it induces ovulation in certain mammal species.

Although it has been seen that this could occur in animals such as llamas, in humans it is not so clear whether it can exercise any kind of real function or whether it is a phenomenon that once had its biological importance but is now somewhat vestigial.

5. Romantic love

It has been seen that people who have been in a love relationship for a period of no more or less than one year have higher concentrations of nerve growth factor than in subjects who are single or have had a partner for longer.

NGF can indirectly stimulate the expression of adrenocorticotrophic hormone (ACTH) in the hypothalamic-pituitary-adrenal axis, increasing vasopressin secretion.

In turn, ACTH stimulates the secretion of cortisol, a stress hormone. Increased cortisol in the blood can induce emotions such as euphoria, which coincides with the first symptoms of romantic love.

Research results

In animal models, nerve growth factor has been shown to prevent and reduce damage from degenerative diseases. NGF promotes nerve regeneration in rats. In addition, in inflammatory diseases, NGF is increased, having the function of reducing the symptoms of inflammation .

It has also been shown that it could be involved in the repair of myelin, the substance that protects the inside of the neuron, where the nerve impulse travels. This is why the use of nerve growth factor has been proposed as a treatment to treat and prevent multiple sclerosis. It has also been considered for use in psychiatric disorders such as dementia, depression, schizophrenia, anorexia and bulimia nervosa, autism spectrum disorders and Rett syndrome.

1. Alzheimer’s disease

Problems in emitting neuron maintenance signals when NGF is coupled have been linked to Alzheimer’s disease.

That is why it has been proposed, as a therapeutic tool, to incorporate into the brain of patients connective tissue cells genetically modified to secrete nerve growth factor, promoting the growth of new neural fibers.

This treatment with connective cells has been seen to be useful in rescuing nerve cells that were vulnerable to dying from the disease.

In some patients it has been seen that the therapeutic effects of the treatment lasted almost ten years after the application of the treatment. The nerve cells managed to maintain a healthy size, and signals were activated to promote their survival.

2. Schizophrenia

Stress and anxiety are precipitating factors in many mental disorders reported in the DSM-5, and research suggests that a mood influenced by these two emotions affects NGF levels, as well as impairing cognitive functions . Bearing this in mind, it makes sense that cognitive impairment could be seen in patients with schizophrenia.

It has been seen that patients with this disorder, once treated with atypical antipsychotics, their NGF levels increase, although this effect has not been seen in those who are treated with typical antipsychotics. Patients with atypical antipsychotics show a more significant cognitive improvement compared to those not receiving that medication.

The fact that NGF is involved in the reduction of the negative symptoms of schizophrenia has also been related.

3. Rett syndrome and ASD

In Rett syndrome and autism spectrum disorders (ASD), there are certain differences in the levels of nerve growth factor that can be found in various areas of a patient’s nervous system.

Lower levels of NGF in the spinal fluid have been observed in patients with Rett compared to autistic patients, who have properly normal levels.

Pharmacological therapies to regulate NGF in people with Rett syndrome have been shown to be effective , especially in areas such as motor control and cortical functioning. In addition, this type of treatment improves social communication.

4. Bipolar disorder

In bipolar disorder, altered neurotrophin levels have been shown to cause problems with brain plasticity. Patients with the disorder have been shown to have reduced levels of NGF , especially in the manic phase . This leads to an irritable mood, increased energy and less subjective need for sleep.

Low levels of nerve growth factor can be used as a biomarker to know the current status of the patient.

Patients with bipolar disorder treated with lithium have higher concentrations of NGF in the prefrontal cortex, the limbic system, the hippocampus and the amygdala.

Bibliographic references:

  • Aloe, L., Rocco, M. L., Balzamino, B. O., & Micera, A. (2015). Nerve Growth Factor: A Focus on Neuroscience and Therapy. Current neuropharmacology, 13(3), 294-303. doi:10.2174/1570159×13666150403231920
  • Freeman R. S., Burch R. L., Crowder R. J., Lomb D. J., Schoell M. C., Straub J. A., Xie L. (2004). “NGF deprivation-induced gene expression: after ten years, where do we stand? Progress in Brain Research. 146: 111-26. doi:10.1016/S0079-6123(03)46008-1
  • Sanes DH, Thomas AR, Harris WA (2011). “Naturally-occurring neuron death.” Development of the Nervous System, Third Edition. Boston: Academic Press. pp. 171-208. ISBN 978-0-12-374539-2
  • Pierucci D, Cicconi S, Bonini P, Ferrelli F, Pastore D, Matteucci C, Marselli L, Marchetti P, Ris F, Halban P, Oberholzer J, Federici M, Cozzolino F, Lauro R, Borboni P, Marlier LN (2001) “NGF-withdrawal induces apoptosis in pancreatic beta cells in vitro”. Diabetology. 44 (10): 1281-95. doi:10.1007/s00125010065
  • Ratto MH, Leduc YA, Valderrama XP, van Straaten KE, Delbaere LT, Pierson RA, Adams GP (Sep 2012) “The nerve of ovulation-inducing factor in semen”. Proceedings of the National Academy of Sciences of the United States of America. 109 (37): 15042-7. doi:10.1073/pnas.1206273109