Neurotrophins: What They Are, Functions And What Types There Are
Neurotrophins are a group of proteins that are responsible for our nervous system functioning correctly maintenance and healing 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.
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 They are able to induce the emission of signals for certain types of cells and make them survive in addition to inducing the processes by which they make cells have different functions, that is, they differentiate.
Although most 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.
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 pathways that do not provide any type of benefit as they are poorly formed or incomplete.
But this does not mean that the subject has cognitive problems or their intellectual capacity is impaired. It is in this phase in which the neurons that are still developing form axons that connect with the target cells, causing brain circuits to form that are of real use for the functioning of the individual. These cells control the secretion of various types of neurotrophic factors that ensure that the neuron can survive
Among these factors can be found nerve growth factor, a protein that stimulates the division and differentiation of neurons in the sympathetic nervous system and also sensory neurons. 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 entire process of survival of neurons would not be possible if they did not have two types of receptors attached to their cell membranes, in which neurotrophins are coupled. These two receptors are p75, to which all types of neurotrophins can be coupled, and several subtypes of the Track or Trk receptor, which are more selective.
Types of neurotrophins
Below we will briefly see the main types of neurotrophins.
1. Nerve growth factor (NCF 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 TrkA type receptors.
2. Brain-derived neurotrophic factor (BDNF)
Brain-derived neurotrophic factor (BDNF) is found primarily 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 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 seen in animal models that this factor greatly stimulates neurogenesis.
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 the BDNF, given that 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 primarily coupled to the TrkB receptor.
5. DHEA and DHEA sulfate
Dehydroepiandrosterone (DHEA) and its sulfate version, DHEA-S, have been shown to act as high-affinity TrkA and p75 receptor agonist molecules
As they have a similar chemistry to 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 type receptors, although if they bind 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 must have had 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 conservation of nerve cells, in addition to their survival and differentiation, it has also been seen that they act during the process that puts an end to the life of these cells: apoptosis.
Just like any other cell, neurons are programmed to die at some point. Neurotrophic signals that promote the survival of neurons are mediated by high-affinity Trk receptors, while apoptotic signals, that is, 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 could 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 the development of the central and peripheral nervous systems, neurotrophins that couple to the p75 receptor, once they have attached to them, activate multiple intracellular pathways with which they regulate the apoptosis process. It may 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. On the other hand, if 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 nervous system it is more neurotrophic factors that decide which cells should die. It is in this system where 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 than survival function.
