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

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

We are going to 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.

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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 to inducing the processes by which they cause cells to have different functions, that is, to differentiate themselves.

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 are responsible for regulating this process.

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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 nervous impulse from going through ways that do not suppose any type of benefit as 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 in this phase that the developing neurons still form axons that connect with the cells. objective, causing brain circuits to be formed that represent a real utility for the functioning of the individual. 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 neurons of the sympathetic nervous system and also the sensory ones. In neurons that are part of the central and peripheral nervous system, neurotrophins they acquire 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 they did not have attached to their cell membranes are two types of receptors, in which neurotrophins couple. These two receptors are p75, to which all types of neurotrophins can be attached, and several subtypes of the Track or Trk receptor, which are more selective.

Types of neurotrophins

Next we will see very briefly the main types of neurotrophins.

1. Nerve growth factor (FCN or NGF)

Nerve growth factor is a protein that is secreted by the target cell of a neuron. As we were already saying, this substance is essential 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 like TrkA.

2. Brain-derived neurotrophic factor (BDNF)

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

Activates certain types of neurons, both central and peripheral, helping their survival and fostering 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, the cerebellum and the hippocampus. These areas are very important for learning, thinking, and memory. This factor has been shown to stimulate neurogenesis quite a bit in animal models.

• You may be interested: "Brain Derived Neurotrophic Factor (BDNF) - What is it?"

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 performs similar functions to BDNF, since it also induces the differentiation of new neurons.

4. Neurotrophin-4 (NT-4)

It performs functions similar to that of its relative, the NT-3. It is mostly coupled to the TrkB receiver.

5. DHEA and DHEA sulfate

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

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

It has been seen 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.

DHEA has been hypothesized to be a kind of ancestral molecule for the Trk receptor, that it had to exert some important function in the first species that had a nervous system.

Role of neurotrophins in cell apoptosis

Like neurotrophins, they 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 the survival of neurons are mediated by high-affinity receptors Trk, while apoptotic signals, that is, those that induce cell death, are mediated by receptors p75.

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 both central and peripheral nervous system development, neurotrophins that bind to the receptor p75, once they have attached to these, 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. On the other hand, if the nerve growth factor (NGF) is coupled to these receptors, programmed cell death is prevented.

In the peripheral nervous system, the decision of 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.

On the other hand, in the central one, more neurotrophic factors decide which cells should die. It is in this system where the neurotrophic factor derived from the brain is found, especially in the substantia nigra, the amygdala, the hypothalamus, cerebellum, cortex, hippocampus, and spinal cord. It must be said that it is in the central nervous system that neurotrophic factors seem to play a maintenance role rather than survival.

Bibliographic references:

• Henderson, C. AND. (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. TO.; 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