Neurotrophin
Neurotrophin | |||||||||
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Neurotrophins are a family of
They belong to a class of
Although the vast majority of neurons in the mammalian brain are formed prenatally, parts of the adult brain (for example, the hippocampus) retain the ability to grow new neurons from neural stem cells, a process known as neurogenesis.[4] Neurotrophins are chemicals that help to stimulate and control neurogenesis.
Terminology
According to the
Function
During the development of the vertebrate nervous system, many neurons become redundant (because they have died, failed to connect to target cells, etc.) and are eliminated. At the same time, developing neurons send out axon outgrowths that contact their target cells.[8] Such cells control their degree of innervation (the number of axon connections) by the secretion of various specific neurotrophic factors that are essential for neuron survival. One of these is nerve growth factor (NGF or beta-NGF), a vertebrate protein that stimulates division and differentiation of sympathetic and embryonic sensory neurons.[9][10] NGF is mostly found outside the central nervous system (CNS), but slight traces have been detected in adult CNS tissues, although a physiological role for this is unknown.[8] It has also been found in several snake venoms.[11][12]
In the peripheral and central neurons, neurotrophins are important regulators for survival, differentiation, and maintenance of nerve cells. They are small proteins that secrete into the nervous system to help keep nerve cells alive. There are two distinct classes of
Receptors
There are two classes of receptors for neurotrophins: p75 and the "Trk" family of Tyrosine kinases receptors.[13]
Types
Nerve growth factor
Nerve growth factor (NGF), the prototypical
Brain-derived neurotrophic factor
Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor found originally in the
BDNF is one of the most active substances to stimulate neurogenesis. Mice born without the ability to make BDNF suffer developmental defects in the brain and sensory nervous system, and usually die soon after birth, suggesting that BDNF plays an important role in normal
Despite its name, BDNF is actually found in a range of tissue and cell types, not just the brain. Expression can be seen in the retina, the CNS, motor neurons, the kidneys, and the prostate. Exercise has been shown to increase the amount of BDNF and therefore serve as a vehicle for neuroplasticity.[15]
Neurotrophin-3
Neurotrophin-3, or NT-3, is a neurotrophic factor, in the NGF-family of neurotrophins. It is a protein growth factor that has activity on certain neurons of the peripheral and central nervous system; it helps to support the survival and differentiation of existing neurons, and encourages the growth and differentiation of new neurons and synapses. NT-3 is the third neurotrophic factor to be characterized, after NGF and BDNF.
NT-3 is unique among the neurotrophins in the number of neurons it has potential to stimulate, given its ability to activate two of the receptor tyrosine kinase neurotrophin receptors (
Neurotrophin-4
Neurotrophin-4 (NT-4) is a neurotrophic factor that signals predominantly through the
DHEA and DHEA sulfate
The
Role in programmed cell death
In the development of both the
The expression of TrkA or TrkC receptors in the absence of neurotrophins can lead to apoptosis, but the mechanism is poorly understood.[31] The addition of NGF (for TrkA) or NT-3 (for TrkC) prevents this apoptosis.[31] For this reason TrkA and TrkC are referred to as dependence receptors, because whether they induce apoptosis or survival is dependent on the presence of neurotrophins.[22][32] The expression of TrkB, which is found mainly in the CNS, does not cause apoptosis.[22] This is thought to be because it is differentially located in the cell membrane while TrkA and TrkC are co-localized with p75NTR in lipid rafts.[22][31]
In the PNS (where NGF, NT-3 and NT-4 are mainly secreted) cell fate is determined by a single growth factor (i.e. neurotrophins).[24][32] However, in the CNS (where BDNF is mainly secreted in the spinal cord, substantia nigra, amygdala, hypothalamus, cerebellum, hippocampus and cortex) more factors determine cell fate, including neural activity and neurotransmitter input.[24][32] Neurotrophins in the CNS have also been shown to play a more important role in neural cell differentiation and function rather than survival.[32] For these reasons, compared to neurons in the PNS, neurons of the CNS are less sensitive to the absence of a single neurotrophin or neurotrophin receptor during development; with the exception being neurons in the thalamus and substantia nigra.[22]
Gene knockout experiments were conducted to identify the neuronal populations in both the PNS and CNS that were affected by the loss of different neurotrophins during development and the extent to which these populations were affected.[22] These knockout experiments resulted in the loss of several neuron populations including the retina, cholinergic brainstem and the spinal cord.[22][24] It was found that NGF-knockout mice had losses of a majority of their dorsal root ganglia (DRG), trigeminal ganglia and superior cervical ganglia.[22][28] The viability of these mice was poor.[22] The BDNF-knockout mice had losses of a majority of their vestibular ganglia and moderate losses of their DRG,[33] trigeminal ganglia, nodose petrosal ganglia and cochlear ganglia.[22][28] In addition they also had minor losses of their facial motoneurons located in the CNS.[22][28] The viability of these mice was moderate.[22] The NT-4-knockout mice had moderate losses of their nodose petrosal ganglia and minor losses of their DRG, trigeminal ganglia and vestibular ganglia.[22][28] The NT-4-knockout mice also had minor losses of facial motoneurons.[22][28] These mice were very viable.[22] The NT-3 knockout mice had losses of a majority of their DRG, trigeminal ganglia, cochlear ganglia and superior cervical ganglia and moderate losses of nodose petrosal ganglia and vestibular ganglia.[22][28] In addition the NT-3-knockout mice had moderate losses of spinal moroneurons.[22][28] These mice had very poor viability.[22] These results show that the absence of different neurotrophins result in losses of different neuron populations (mainly in the PNS).[22] Furthermore, the absence of the neurotrophin survival signal leads to apoptosis.[22]
See also
References
- PMID 16472198. Archived from the originalon 2009-08-30. Retrieved 2020-04-16.
- PMID 16939974.
- S2CID 9507693.
- PMID 9809557.
- ^ Neurotrophins at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- ^ ISBN 9780071481274.
Neurotrophic factors are polypeptides or small proteins that support the growth, differentiation, and survival of neurons. They produce their effects by activation of tyrosine kinases.
- ^ Sanes, Dan H.; Reh, Thomas A.; Harris, William A. (2012). Development of the Nervous System. Academic Press. pp. 173–193.[ISBN missing]
- ^ PMID 2369898.
- PMID 3589669.
- PMID 8488558.
- PMID 1477101.
- PMID 1995338.
- S2CID 23869093.
- S2CID 29211700.
- ^ "Exercise builds brain health: key roles of growth factor cascades and inflammation" by Carl W. Cotman, Nicole C. Berchtold and Lori-Ann Christie https://scholar.google.com/scholar?cluster=11830727319998892361&hl=en&as_sdt=0,10
- ^ "Entrez database entry for NT-4/5". NCBI. Retrieved 2007-05-07.
- ^ PMID 26908835.
- PMID 21541365.
- ^ PMID 25330101.
- S2CID 26914550.
- ^ a b c d e f g h i Sanes, Dan H.; Reh, Thomas A.; Harris, William A. (2012). Development of the Nervous System. Academic Press. pp. 173–193.
- ^ ISBN 978-0-12-385870-2.
- PMID 9472042.
- ^ S2CID 15915753.
- S2CID 205222117.
- ^ PMID 20186707.
- ^ PMID 18931691.
- ^ PMID 11520916.
- S2CID 33597483.
- PMID 9547236.
- ^ PMID 24217616.
- ^ S2CID 16624509.
- S2CID 20325630.
External links
- DevBio.com – 'Neurotrophin Receptors: The neurotrophin family consists of four members: nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and neurotrophin 4 (NT-4)' (April 4, 2003)
- Dr.Koop.com – 'New Clues to Neurological Diseases Discovered: Findings could lead to new treatments, two studies suggest', Steven Reinberg, HealthDay (July 5, 2006)
- Helsinki.fi – 'Neurotrophic factors'
- Neurotrophins at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- [1] – Neurotrophin-3 image