Neurotrophins: what are they, what are their functions and what types are there?

What are neurotrophins and what functions do they perform in the nervous system? Let's take a look.

Neurotrophins are a group of proteins that are responsible for the proper functioning of our nervous system, maintenance and healing of the cells that make up our brain.They are responsible for the maintenance and healing of 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 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 set of growth factors, substances which are able to induce the emission of signals for certain types of cells and make them able to survive.In addition, they induce the processes by which they cause cells to have different functions, i.e., to 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 in charge of regulating 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.. That is why it is necessary to eliminate them, to save space and prevent the nerve impulse from going through pathways that do not provide any benefit because they are poorly formed or incomplete.

But this does not mean that the subject has cognitive problems or his intellectual capacity is impaired. It is at this stage that the neurons that are still developing form axons that connect with the target cells, causing brain circuits to form that are of real use to the individual's functioning. These cells control the secretion of several 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 neurons of the sympathetic nervous system and sensory neurons. In the neurons that form part of the central and peripheral nervous system, neurotrophins important role in regulating the processes of maintenance, survival and differentiation of these nerve cells. of these nerve cells.

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

Types of neurotrophins

In the following we will look very briefly at the main types of neurotrophins.

1. Nerve growth factor (NGF or NGF)

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

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

2. Brain-derived neurotrophic factor (BDNF)

Brain-derived neurotrophic factor (BDNF) is found primarily 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 them to survive and promotes their survival.It activates certain types of neurons, both central and peripheral, aiding their survival and promoting their growth and differentiation. It also enhances the appearance 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 shown in animal models that this factor stimulates neurogenesis quite a bit.

3. 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 exerts similar functions to BDNF in that it also induces the differentiation of neurons in the central and peripheral nervous system. it also induces the differentiation of new neurons..

4. Neurotrophin-4 (NT-4)

It exerts similar functions to its relative NT-3. It is mainly coupled to the TrkB receptor.

5. DHEA and DHEA sulfate

Dehydroepiandrosterone (DHEA) and its sulphate version, DHEA-S, have been shown to exert as high affinity TrkA and p75 receptor agonist molecules..

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

It has been shown that DHEA can also bind to TrkB and TrkC receptors, although if they bind to the latter the former cannot be activated in the process.

It has been hypothesized that DHEA is a sort of an ancestral molecule for the Trkreceptor, which must have had some important function in the first species to have 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 shown 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, at some necessary time, die. Neurotrophic signals that promote neuronal survival are mediated by high-affinity Trk receptors, whereas 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 roleThe programmed destruction of nerve cells has a very important biological role, which is to avoid a massive production of neurons that may 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 systems, neurotrophins that couple to the p75 receptor, once they have attached to them, activate multiple intracellular pathways by which they regulate the process of apoptosis. It can also happen that the expression of TrkA and TrkC receptors, in the absence of neurotrophins, induces apoptosis, although it is not known exactly how this process occurs. In contrast, if nerve growth factor (NGF) is coupled to these receptors, programmed cell death is prevented.

In the peripheral nervous system, the decision as to whether nerve cells live or die depends exclusively 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 nervous system it is more the neurotrophic factors that decide which cells should die. It is in this system that the brain-derived neurotrophic factor is found, especially in the substantia nigra, amygdala, hypothalamus, cerebellum, cortex, hippocampus and spinal cord. It should be said that it is in the central nervous system where neurotrophic factors seem to exert more of a maintenance function than a survival function.

Bibliographical 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.