Neurotrophins are a group of proteins that allow our nervous system to function properly., Maintain and disinfect the cells that make up our brain and nerves.
Let’s see exactly what they are, how they work, what types there are and 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 that induce the survival, growth and proper functioning of nerve cells.
They belong to a group 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 say to differentiate.
Although most of the nerve cells found in mammals form during the prenatal period, parts of the brain, such as the hippocampus, can develop new neurons when the individual is already formed. These new neurons come from neural stem cells. This process of creating new nerve cells is called neurogenesis., And neurotrophins are the substances 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, save space and prevent the nerve impulse from proceeding in a way that does not mean any benefit by being malformed or incomplete.
But this does not mean that the subject has cognitive problems or that his intellectual capacity is impaired. It is at this stage that developing neurons again form axons which connect to target cells, causing the formation of brain circuits which are of real use to the functioning of the individual. These cells control the secretion of various types of neurotrophic factors that ensure the survival of the neuron..
Among these factors is nerve growth factor, a protein that stimulates the division and differentiation of neurons in the sympathetic and sensory nervous system. In neurons that are part of the central and peripheral nervous system, neurotrophins they play a very important role in the regulation of maintenance, survival and differentiation processes of these nerve cells.
However, this whole process of neuron survival wouldn’t be possible if they didn’t have two types of receptors attached to their cell membranes, in which neurotrophins bind. These two receptors are p75, in which all types of neurotrophins can be coupled, and several receptor subtypes or Trk receptors, which are more selective.
Types of neurotrophins
Below we will take a very brief look at the main types of neurotrophins.
1. Nerve growth factor (FCN or NGF)
The nerve growth factor is a protein secreted by the target cell of a neuron. As we said, this substance is essential for sympathetic and sensory neurons, ensuring their survival and maintenance.
This factor is released by a cell in the neuron, in which there will be high affinity TrkA-type receptors.
2. Brain-derived neurotrophic factor (BDNF)
Brain-derived neurotrophic factor (BDNF) is mainly found in the brain, but can also be found in other parts of the body.
It activates certain types of neurons, both central and peripheral, Help their survival and promote their growth and differentiation. It also improves the appearance of synapses due to the fact that it induces the growth of axons and dendrites.
It is particularly active in parts of the brain such as the cortex, cerebellum and hippocampus. These areas are very important for learning, thinking and memory. This factor has been seen in animal models to greatly stimulate 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 BDNF, because it also induces the differentiation of new neurons.
4. Neurotrophin-4 (NT-4)
It performs similar functions to its NT-3 parent. It mainly attaches to the TrkB receiver.
5. DHEA and DHEA sulfate
Dehydroepiandrosterone (DHEA) and its sulfate version, DHEA-S, have been shown to they act as agonist molecules of high affinity TrkA and p75 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 shown that DHEA can also bind to TrkB and TrkC-like receptors, although if they bind to the latter, the former cannot be activated in the process.
DHEA was thought to be a species of ancestral molecule for the Trk receptor, Which was to play an important role in the first species which 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 shown to work during the process that terminates the life of nerve cells. These cells: apoptosis.
As with any other cell, neurons are programmed to die at some point. Neurotrophic signals that promote neuronal survival are 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 plays a very important biological role, Which consists of avoiding a massive production of neurons that can hinder optimal functioning of the brain. In the process, most of the cells that die are neuroblasts and neurons that have failed to functionally develop.
In the development of the central and peripheral nervous systems, neurotrophins that bind to the p75 receptor, once attached to them, activate multiple intracellular pathways with which they regulate the process of apoptosis. It may also happen that the expression of the 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 these receptors are coupled to nerve growth factor (NGF), 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 are mainly neurotrophins 3 (NT-3) and 4 (NT-4).
In contrast, at the center, it is more 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 noted that it is in the central nervous system that neurotrophic factors seem to play a more maintenance role than survival.
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