Introduction
The human brain is a very complex structure. Billions of neurons work together to create a symphony of emotions and thoughts. It shows the incredible achievements that occur when the neurons develop and mature. This intricate process lays the foundation for the existence of the human race. It is achieved by several essential molecules, that have their vital roles to accomplish. Among these molecules belong a group of proteins called ‘neutrophins’. This article deals with the role played by neurotrophins in nerve development.
What Are Neurotrophins?
Neurotrophins belong to a family of proteins and are responsible for nerve cells' growth, survival, and functioning. It is a type of growth factor (a naturally occurring substance that stimulates the growth and proliferation of cells). It signals the selected cells to proliferate, differentiate, or survive. The growth factors that help neuron's survival are also called neurotrophic factors.
Certain tissues produce neurotrophic factors, which prevent initiating the apoptosis (cell death) of the neuron associated, thereby prolonging the life of the neuron. In addition, the neurotrophins also stimulate the progenitor cells to differentiate into neurons. The brain's limbic region (the part of the brain responsible for emotions, memory, and arousal) retains its ability to produce new neurons from the neural cells. This process is called neurogenesis. These molecules function during the embryonic developmental stage and throughout adulthood. They bind to certain receptors in the nerve membrane and initiate the process.
What Are the Types of Neurotrophins?
There are four types of neurotrophins. They include:
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Nerve Growth Factor (NGF): It is a protein secreted by the neuron’s target cell. It is the first of the growth factors to be discovered. It plays an important role in the maintenance and survival of the sensory (neurons that carry information from the environment to the central nervous system (CNS) and sympathetic (neurons in the sympathetic nervous system which is responsible for fight-flight response) neurons. NGF released from the target cell enters the neuron through its high-affinity receptor and activates it. This complex is then transported back to the cell body of the neuron.
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Brain-Derived Neurotrophic Factor (BDNF): This factor is usually found in the brain and sometimes in the periphery. It is a protein found in certain central and sympathetic nervous system neurons. It promotes the development and differentiation of new neurons and synapses (the gap between neurons that help in transferring signals) and helps the existing neurons to survive through axonal and dendritic sprouting (the process in which the ends of the axon or dendrite produces fine nerve fibers). It was the second neurotrophin to be discovered. It is active in the brain's basal forebrain, cortex, hippocampus, and cerebellum, responsible for memory, thinking, and learning. It is one of the most effective substances for neurogenesis. Hence, it plays an important role in neural development. Studies show mice born without this factor had defects in the brain and sensory nervous systems. They were found to die soon after birth. In addition to the brain, BDNF is also found in the retina, kidneys, and prostate. Studies show that exercise helps to increase the amount of BDNF in the body.
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Neurotrophin-3 (NT-3): It is the third neurotrophic factor to be discovered. It is a protein that acts on certain central and sympathetic nervous system neurons. It promotes the development and differentiation of new neurons and synapses and helps differentiate existing neurons. It differs from the other neurotrophins in the number of neurons it can activate. It can activate two neurotrophin receptors. Studies in mice that lack this neurotrophin showed a lack of mechanoreceptive (the ability to detect stimuli like touch, sound, and changes in posture) and proprioceptive (the ability to respond to the position and movement of the body) sensory neurons.
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Neurotrophin-4 (NT- 4): It is a neurotrophin that transfers signals through the TrkB receptor tyrosine kinase (a surface receptor). It is also known by other names like NT4, NT5, NTF4, and NT-4/5.
What Is the Role of Neurotrophins in Neuronal Development?
The neurotrophin plays an important role in a neuron's growth, differentiation, and existence. It also involves the neuron's programmed cell death (apoptosis). Numerous intracellular pathways that are crucial for controlling apoptosis are activated when the neurotrophin-binding neurotrophin receptor p75NTR binds to neurotrophin during the development of the peripheral and central nervous systems.
The NGF, N-3, and N-4 are mainly secreted in the peripheral nervous system (PNS). The neurotrophins determine the cell’s fate here. However, the fate of the cell is determined by a number of elements within the central nervous system, such as neuronal activity or the input of neurotransmitters. In the central nervous system, neurotrophins are more crucial for cell differentiation than for cell survival. Hence, the neurons in the CNS are less susceptible to the absence of a single neurotrophin or neurotrophin receptor during development than neurons in the PNS.
The neurons in the thalamus and substantia nigra are an exception. It has been proved that NGF affects the migration of Schwann cells (a type of cells around the neurons that produce myelin sheath, the protective covering of a neuron) in the PNS and oligodendrocytes (cells that produce myelin sheath) in the CNS. The stimulation of neutrino outgrowth (a method to study the development and degeneration of neurons in vitro) is another effect of the NGF. NGF signaling promotes the development of neurons and astrocytes but not oligodendrocytes. The effects of BDNF are controversial. Studies show that surface receptors like TrkB isoforms and p75NTR interact with other variables to influence BDNF-induced neurogenesis.
Conclusion
Neurotrophins have been linked to neurodegenerative (conditions that destroy the motor neurons) and psychiatric disorders, in addition to their role in neuronal development. Studies show that conditions like Alzheimer’s disease, Parkinson’s disease, depression, etc. are linked to the disruption of the neurotrophin and their receptors. Therefore, it is important to understand the complex nature of neurotrophin signaling to identify potential treatments for these conditions. Additional research into neurotrophins can potentially solve the challenges around neuronal development and pave the way for novel therapeutic approaches for many degenerative and psychiatric disorders.
