Neurotrophic Factors

What are neurotrophins?

Neurotrophins are a family of growth factors that serve to promote the growth and survival of neurons. They are large protein molecules produced by the nervous system cells that regulate cell division, cell survival, and neurite outgrowth. During the nervous system development, neurotrophins are secreted by nerve target cells or surrounding glia, and only the neurons that are receiving sufficient amounts of neurotrophin will survive. For example, the neurotrophin Nerve Growth Factor (NGF) is well known among the neurotrophic agents to have the capicity to direct survival and differentiation of sympathetic cells in the Peripheral Nervous System. Most of these growth factors are already being licensed for use in humans. They are used for administering opiods for chronic pain management and are found in antispasticity drugs that are used for spinal cord injury.

Because neurotrophins are known to promote nerve cell growth and survival, there has been a great deal of research done on using neurotrophins as a possible therapy for people suffering from disorders involving neuronal degeneration and physical trauma resulting in the severing of nerve connections. They can help direct and facilitate the survival of neurons after physical injury (i.e., motorcycle accidents and sports-related injuries) or in neurodegenerative diseases such as Alzhiemer's, Huntington's, and Parkinson's Disease. By applying these growth factors, primarily in the Central Nervous System area where neurons have more difficulty in repairing themselves (in comparison to the better repair capabilities of the Peripheral Nervous System), researchers today hope to make neurotrophins a more widely accepted clinical possibility in the field of neuroregeneration.


Source: http://www.cryst.bbk.ac.uk/~ubcg09j/neurotrophins/beta.html

How do neurotrophic factors work?

Neurotrophins will bind to a specific tyrosine kinase (trk) receptor on a nerve terminal, which will induce dimerization and auto-phosphorylation of receptor molecules, which leads to endocytosis of the receptor-neurotrophin complex. The vesicle that contains the complex is then transported by dynein along various microtubules up to the axon and to the soma (This is done by way of retrograde flow). Along the way, the complex will initiate a signal transduction cascade that ultimately inhibits the genes for apoptosis (programmed cell death), thus keeping the neuron cell alive.

What are the types of neurotrophic factors?


Source: Neotherapeutics, Inc.

There are a variety of neurotrophic factors that have been identified and studied today. Each type of growth factor has a specific function, but still contributes overall to promoting the survival and proliferation of neurons. The following isa classification of the types of neurotrophins that are out there:

a) Nerve Growth Factor (NGF): This neurotrophin is vital for the development and the maintainance of both central and peripheral nervous system neurons. NGF has been known to play a key role in preventing neuronal degeneration, and has been seen to show renewed neuronal cell growth in laboratory tests involving rats with severed sensory nerves.


Chemical Structure for NGF
Source: http://www.crust.bbk.ac.uk/~ubcgo09j/neurotrophins/nt_gallery/pn1_1.html

b) Neurotrophin-3 (NT-3): This factor stimulates nerve growth in different populations of neurons outside of the population being affected by NGF. It has also been run in several clinical trials and is equally important to central and peripheral neurons.

c) Fibroblast Growth Factor, basic (bFGF): The neurotrophin is important for the initiation of nerve repair after trauma or injury. It also is known to promote the proliferation of immature neurons (those with stunted growth), and causing the multiplication of new neurons. This growth factor is primarily found in the Central Nervous System and the brain, and is responsible for stimulating neurite outgrowth of cells in the cortex, striatum, hippocampus, cerebellum, parasympathetic ganglia, and the spinal cord. During periods of neuronal injury (i.e., cerebral ischemia), the expression of bFGF is significantly increased. Researchers have also found bFGF to have the capacity to promote regeneration in severed optic nerves.

d) Others: brain-derived neurotrophic factor (BDNF), insulin-like growth factor (IGF), ciliary neurotrophic factor (CNTF), neurotrophic factor-4/5 (NT-4/5). Not as much is known about these growth factors, as they are still being clinically investigated and studied.