Neurotrophic Factors


Scientists have recently discovered a family of proteins called neurotrophic factors. These substances are responsible for the growth and survival of neurons during development, and for maintaining adult neurons. Neurotrophic factors also are capable of making damaged neurons regrow their processes in a test tube and in animal models. Because of this, they represent exciting possibilities for reversing devastating brain disorders, including Alzheimer's disease, Parkinson's disease and Lou Gehrig's disease.
For decades, scientists believed that brain cells of the central nervous system could not regrow following damage due to trauma such as head injury or disorders such as Alzheimer's disease. Treatments did not exist. The outlook was bleak.
But now that thinking has been turned upside down. Scientists recently have discovered a whole family of proteins called neurotrophic factors -- derived from the Greek "neuro" for nerve and "troph" for nourish. These proteins play a crucial role in the development and survival of nerve cells, or neurons, and in supporting adult neurons to keep them healthy throughout life.

Recent research shows that neurotrophic factors are:

Present in early development of the nervous system and are responsible for the initial growth and development of neurons in the peripheral and central nervous systems.
Released by target tissue of a growing neuron and can determine whether a neuron reaches its target during development; neurons which do not reach the target die.
Capable of making damaged neurons regrow their processes in a test tube and in animal models and, thus, represent exciting possibilities for reversing devastating disorders, including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease.
Scientists are now looking for ways to harness neurotrophic factors to induce the regrowth of damaged neurons and improve symptoms of patients with neurological diseases. Neurotrophic factors exert their effects on neurons through several receptors -- proteins on the surface of cells into which neurotrophic factors fit much the way a key fits a lock.

Neurotrophic factors, produced by several body tissues including muscle, act by attaching to receptors on the tips, or nerve terminals, and on the cell body -- which contains the nucleus -- of neurons. The signal can then be carried through the axon, the neuron's elongated fiberlike extension, which can be as long as a yard, to the cell body where it tells the cell what to do.

Thus far, scientists have identified several neurotrophic factor receptors -- which also may be potential targets for therapy. A receptor called trk is required for the action of nerve growth factor (NGF), the first neurotrophic factor, which was discovered 40 years ago. NGF affects primarily neurons using the neurotransmitter acetylcholine in the basal forebrain, sensory neurons and sympathetic neurons that regulate organs such as the heart and lungs. Relatives of trk are receptors for other neurotrophic factors -- trkB seems to be a receptor for brain-derived neurotrophic factor; and trkC for neurotrophin-3.
Scientists continue to match up various neurotrophic factors and their possible roles in maintaining neurons and in neurological disorders. Meanwhile, ciliary neurotrophic factor, insulin-like growth factor-1 and brain-derived neurotrophic factor are in human clinical trials for treating ALS.
These patients may be among the first to benefit from a therapeutic neurotrophic factor because treatment for ALS does not need to cross the blood-brain barrier. Since ALS involves the loss of motor neurons whose axons are located in the peripheral nervous system, drugs can be delivered by injection. Success with these investigations should encourage scientists to devise treatments for disorders of the central nervous system such as Parkinson's disease and Alzheimer's disease.
While therapeutic agents made from neurotrophic factors are probably three to ten years away, research holds tremendous promise. Moreover, dozens of neurotrophic factors may yet be discovered and these may be important for treating other neurodegenerative disorders and trauma.
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In the brain, a neurotrophic factor is released by a neuron or a support cell, such as an astrocyte, and binds to a receptor on a nearby neuron. This binding results in the production of a signal which is transported to the nucleus of the receiving neuron where it results in the increased production of proteins associated with neuronal survival and function.
Illustration by Lydia Kibiuk, Copyright © 1994 Lydia Kibiuk.


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