Neurotrophins are a group of proteins that are responsible for our nervous system to function properly , maintaining and healing both the cells that make up our brain and our nerves.

We will see exactly what they are, how they work, what types there are and also how, in addition to promoting the survival and growth of the neurons, they induce their programmed death.

What are neurotrophins?

Neurotrophins are a family of proteins which induce the survival, growth and proper functioning of nerve cells.

They belong to a group of growth factors, substances which are capable of inducing the emission of signals for certain types of cells and making them able to survive , as well as inducing the processes by which they make the cells have different functions, that is, they differentiate.

Although most of the nerve cells found in mammals are formed in the prenatal period, some parts of the brain, such as the hippocampus, can grow new neurons when the individual is already formed. These new neurons start from neural stem cells. This process of creating new nerve cells is called neurogenesis , and neurotrophins are the substances that regulate this process.

How do they work?

During postnatal development, many cells of the nervous system, especially neurons, become redundant. Many of them die or have failed to connect with other neurons and target cells . This is why it is necessary to eliminate them, to save space and prevent the nerve impulse from going through pathways that are not beneficial because they are poorly formed or incomplete.

But this does not mean that the subject has cognitive problems or his intellectual capacity is diminished. It is at this stage that the developing neurons still form axons that connect to the target cells, causing brain circuits to form that are of real use to the individual’s functioning. These cells control the secretion of various types of neurotrophic factors that ensure that the neuron can survive .

These factors include nerve growth factor, a protein that stimulates the division and differentiation of the neurons of the sympathetic nervous system and also the sensory neurons. In the neurons that form part of the central and peripheral nervous system, the neurotrophins take on a very important role in regulating the processes of maintenance, survival and differentiation of these nerve cells.

However, this whole process of neuron survival would not be possible if neurons did not have two types of receptors attached to their cell membranes, to which the neurotrophins attach. These two receptors are p75, on which all types of neurotrophins can be coupled, and several subtypes of the Track or Trk receptor, which are more selective.

Types of Neurotrophins

The following is a very brief overview of the main types of neurotrophins.

1. Nerve growth factor (NGF)

Nerve growth factor is a protein that is secreted by the target cell of a neuron . As we were saying, this substance is fundamental for sympathetic and sensory neurons, guaranteeing their survival and maintenance.

This factor is released by a cell towards the neuron, in which there will be high affinity receptors of the TrkA type.

2. Brain-derived neurotrophic factor (BDNF)

Brain-derived neurotrophic factor (BDNF) is found mostly in the brain, but can also be found in other parts of the body.

It activates certain types of neurons, both central and peripheral , helping their survival and promoting their growth and differentiation. It also promotes the emergence of synapses by inducing the growth of axons and dendrites.

It is especially active in parts of the brain such as the cortex, cerebellum and hippocampus. These areas are very important for learning, thinking and memory. It has been seen in animal models that this factor greatly stimulates neurogenesis.

Neurotrophin-3 (NT-3)

Neurotrophin-3 (NT-3) is a neurotrophic factor that promotes the growth of certain neurons in the central and peripheral nervous system. It performs similar functions to BDNF, as it also induces differentiation of new neurons .

4. Neurotrophin-4 (NT-4)

It performs similar functions to its relative the NT-3. It is mainly coupled to the TrkB receiver.

5. DHEA and DHEA sulphate

Dehydroepiandrosterone (DHEA) and its sulfate version, DHEA-S, have been shown to act as agonist molecules of the TrkA and p75 high-affinity receptors .

Since they have a similar chemical affinity to other neurotrophins but are very small in size, these molecules have been called microneurotrophins.

It has been seen that DHEA can also be coupled to receivers type TrkB and TrkC, although if they are coupled to the latter the former cannot be activated in the process.

It has been hypothesized that DHEA is a kind of ancestral molecule for the Trk receptor , which was supposed to exert some important function in the first species that had a nervous system.

Role of neurotrophins in cell apoptosis

Just as neurotrophins play a very important role in the preservation of nerve cells, in addition to their survival and differentiation, they have also been seen to act during the process that puts an end to the life of these cells: apoptosis.

As with any other cell, neurons are programmed to die at some point in time. The neurotrophic signals that promote neuron survival are ‘so mediated by high affinity Trk receptors, while apoptotic signals, i.e. those that induce cell death, are mediated by p75 receptors.

The programmed destruction of nerve cells has a very important biological role , which is to avoid a massive production of neurons that can hinder the optimal functioning of the brain. In the process, most of the cells that die are neuroblasts and neurons that have not developed functionally.

In the development of both the central and peripheral nervous system, the neurotrophins that attach to the p75 receptor, once they have attached themselves to them, activate multiple intracellular pathways with which they regulate the process of apoptosis. It may also happen that the expression of TrkA and TrkC receptors, in the absence of neurotrophins, induce apoptosis, although it is not known exactly how this process occurs. In contrast, if these receptors are coupled to the nerve growth factor (NGF), programmed cell death is avoided.

In the peripheral nervous system, the decision whether nerve cells live or die depends solely on a growth factor . In this part of the nervous system neurotrophins 3 (NT-3) and 4 (NT-4) are mainly found.

In contrast, in the central one, it is more the neurotrophic factors that decide which cells should die. It is in this system that brain-derived neurotrophic factor is found, especially in the substantia nigra, the amygdala, the hypothalamus, the cerebellum, the cortex, the hippocampus and the spinal cord. It can be said that it is in the central nervous system where neurotrophic factors seem to exert a maintenance rather than a survival function.

Bibliographic references:

  • Henderson, C. E. (1996). Role of neurotrophic factors in neuronal development. Current Opinion in Neurobiology. 6 (1): 64-70. doi:10.1016/S0959-4388(96)80010-9
  • Vega, J. A.; García-Suárez, O.; Hannestad, J.; Pérez-Pérez, M.; Germanà, Antonino (2003). “Neurotrophins and the immune system”. Journal of Anatomy. 203 (1): 1-19. doi:10.1046/j.1469-7580.2003.00203.x
  • Huang, E. J., & Reichardt, L. F. (2001). Neurotrophins: roles in neuronal development and function. Annual review of neuroscience, 24, 677-736. doi:10.1146/annurev.neuro.24.1.677