NEUROTROPHINS – NEUROTROPHIC FACTORS
Neurotrophins
or neurotrophic factors are the protein substances, which play an important
role in growth and functioning of nervous tissue.
Source of Secretion
Neurotrophins
are secreted by many tissues in the body, particularly muscles, neuroglial
cells called astrocytes and neurons.
Functions
Neurotrophins:
1.
Facilitate initial growth and development of nerve cells in central and
peripheral nervous system
2. Promote
survival and repair of the nerve cells
3. Play an
important role in the maintenance of nervous tissue and neural transmission.
Recently,
it is found that neurotrophins are capable of making the damaged neurons regrow
their
processes in vitro and in animal models. This indicates the possibilities of
reversing the devastating symptoms of nervous disorders like Parkinson
disease and Alzheimer disease. Commercial preparations of neurotrophins are used for the
treatment of some neural diseases.
Mode of Action
Neurotrophins act via neurotrophin receptors, which are situated at the nerve
terminals and nerve cell body. Neurotrophins bind with receptors and initiate
the phosphorylation of tyrosine kinase.
Types
Nerve
growth factor (NGF) was the first protein substance identified as neurotrophin.
Now, many types
of
neurotophic factors are identified.
NERVE GROWTH FACTOR
Nerve
growth factor (NGF) is a neurotrophin found in many peripheral tissues.
Chemistry
NGF is a
peptide with 118 amino acids. Each molecule of NGF is made up of two α-subunits,
two β-subunits and two γ-subunits. Only the β-subunits have nerve growth-stimulating
activity.
Functions
1. NGF
promotes early growth and development of neurons. Its major action is on
sympathetic
and
sensory neurons, particularly the neurons concerned with pain. Because of its
major action on
sympathetic
neurons, it is also called sympathetic NGF. NGF also promotes the growth of cholinergic
neurons in
cerebral hemispheres.
2.
Commercial preparation of NGF extracted from snake venom and submaxillary
glands of male mouse
is used to
treat sympathetic neuron diseases.
3. NGF
plays an important role in treating many nervous disorders such as Alzheimer
disease,
neuron
degeneration in aging and neuron regeneration in spinal cord injury.
OTHER NEUROTROPHINS
1. Brain-derived
Neurotrophic Growth Factor
Brain-derived
neurotrophic growth factor (BDGF) was first discovered in the brain of pig. Now
it is found in human brain and human sperm. BDGF promotes the survival of
sensory and motor neurons, arising from embryonic neural crest. It also
protects the sensory neurons in peripheral nervous system and motor neurons of pyramidal
system. It enhances the growth of cholinergic, dopaminergic and optic nerves.
It is suggested that BDGF may regulate synaptic transmission. Commercial
preparation is used to treat motor
neuron
diseases.
2. Ciliary
Neurotrophic Factor (CNTF)
CNTF is
secreted in peripheral nerves, ocular muscles and cardiac muscle. It protects
neurons of ciliary
ganglion
and motor neurons.
3. Glial Cell
Line-derived Neurotrophic Factor (GNDF)
GDNF is found
in neuroglial cells. It has a potent protective action on dopaminergic neurons.
It is used
for the
treatment of Parkinson disease.
4. Fibroblast Growth Factor (FGF)
FGF was
first discovered as growth factor promoting the fibroblastic growth. It is also
known to protect the
neurons.
5. Neurotrophin-3
(NT-3)
Neurotrophin-3
(NT-3) acts on γ-motor neurons, sympathetic neurons and neurons from sensory
organs.
It also
regulates the release of neurotransmitter from neuromuscular junction.
NT-3 is
useful for the treatment of motor axonal neuropathy and diabetic neuropathy. Recently,
few more substances belonging to the neurotrophin family such as NT-4, NT-5 and
leukemiainhibiting
factor are
identified. NT-4 and NT-5 act on sympathetic neurons, sensory neurons and motor
neurons.
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