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Information about Neurotrophins

Neurotrophins, also called "neurotrophic factors", are a family of protein which induce the survival of neurons. They belong to a family of growth factors, secreted proteins usually found in the blood stream which are capable of signaling particular cells to survive, differentiate, or grow. Neurotrophic factors are secreted by target tissue and act by preventing the associated neuron from initiating programmed cell death - thus allowing the neurons to survive. Neurotrophins also induce differentiation of progenitor cells, to form neurons.

The neurotrophin family includes nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-1 (NT-1), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4).

Receptors

There are two classes of receptors, p75 and the "Trk" family of Tyrosine kinases receptors.
  • p75 is a low affinity neurotrophin receptor, to which all neurotrophins bind.
  • The Trk family include TrkA, TrkB, and TrkC, and will only bind with specific neurotrophins, but with a much higher affinity. The Trks mediate the functional signals of the neurotrophins.

Nerve growth factor

Main article: Nerve growth factor
Nerve growth factor (NGF), the prototypical growth factor, is a protein secreted by a neuron's target. NGF is critical for the survival and maintenance of sympathetic and sensory neurons. NGF is released from the target cells, binds to and activates its high affinity receptor TrkA, and is internalized into the responsive neuron. The NGF/TrkA complex is subsequently trafficked back to the cell body. This movement of NGF from axon tip to soma is thought to be involved in the long-distance signaling of neurons.

Brain-derived neurotrophic factor

Main article: Brain-derived neurotrophic factor
Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor found originally in the brain, but also found in the periphery. More specifically, it is a protein which has activity on certain neurons of the central nervous system and the peripheral nervous system; it helps to support the survival of existing neurons, and encourage the growth and differentiation of new neurons and synapses through axonal and dendritic sprouting. In the brain, it is active in the hippocampus, cortex, cerebellum, and basal forebrain—areas vital to learning, memory, and higher thinking. BDNF was the second neurotrophic factor to be characterized, after NGF and before neurotrophin-3.

Although the vast majority of neurons in the mammalian brain are formed prenatally, parts of the adult brain retain the ability to grow new neurons from neural stem cells; a process known as neurogenesis. Neurotrophins are chemicals that help to stimulate and control neurogenesis, BDNF being one of the most active. 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 neural development.

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.Neurotrophin self-production by an individual is described in "Keep Your Brain Alive" Workman Publishing 1999

Neurotrophin-1

Neurotrophin-1 (NT-1) is also known as "B cell-stimulating factor-3" (BSF-3) or "cardiotrophin-like cytokine factor 1" (CLCF1), and is a cytokine belonging to the interleukin-6 family. It is a secreted protein, found predominantly in lymph nodes and spleen, which contains 225 amino acids with a molecular mass of 22 kDa in its mature form. It is closely related to other proteins called cardiotrophin-1 and ciliary neurotrophic factor.

NNT-1/BSF-3 induces tyrosine phosphorylation of the IL-6 receptor common subunit glycoprotein 130 (gp130), leukemia inhibitory factor receptor beta, and the transcription factor STAT3. It has been implicated in the induction of IL-1 (via induction of corticosterone and IL-6) and serum amyloid A, and in B cell hyperplasia. This cytokine is capable of B cell activation via gp130 receptor stimulation.[1]

Neurotrophin-3

Main article: Neurotrophin-3
Neurotrophin-3, or NT-3, is a neurotrophic factor, in the NGF-family of neurotrophins. It is a protein growth factor which 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 was the third neurotrophic factor to be characterized, after NGF and BDNF.

Although the vast majority of neurons in the mammalian brain are formed prenatally, parts of the adult brain retain the ability to grow new neurons from neural stem cells; a process known as neurogenesis. Neurotrophins are chemicals that help to stimulate and control neurogenesis. NT-3 is unique in the number of neurons it can potentially stimulate, given its ability to activate two of the receptor tyrosine kinase neurotrophin receptors (TrkC and TrkB - see below). Mice born without the ability to make NT-3 have loss of proprioceptive and subsets of mechanoreceptive sensory neurons. Interestingly, anti-depressant drugs produce behavioural changes mainly through gradual effect on BDNF and desensitisement of autoreceptors.

Neurotrophin-4

Neurotrophin-4 (NT-4) like BDNF, is a neurotrophic factor that signals predominantly through the TrkB receptor tyrosine kinase. It is also known as NT4, NT5, NTF4, and NT-4/5.[2]

References

1. ^ Senaldi et al., Novel neurotrophin-1/B cell-stimulating factor-3: a cytokine of the IL-6 family. Proc Natl Acad Sci U S A. 1999 September 28;96(20):11458-63
2. ^ Entrez database entry for NT-4/5. NCBI. Retrieved on 2007-05-07.
  • Arévalo J, Wu S (2006). "Neurotrophin signaling: many exciting surprises!". Cell Mol Life Sci 63 (13): 1523-37. PMID 16699811. 
  • Hempstead B (2006). "Dissecting the diverse actions of pro- and mature neurotrophins". Curr Alzheimer Res 3 (1): 19-24. PMID 16472198. 
  • Allen S, Dawbarn D (2006). "Clinical relevance of the neurotrophins and their receptors". Clin Sci (Lond) 110 (2): 175-91. PMID 16411894. 

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'
  • MeSH Neurotrophins
 •  • [ e]
Cell signaling, nervous tissue: neurotrophin
GFLGDNF - Neurturin - Artemin - Persephin
OtherBDNF - CNTF - GMF - NGF - Neuregulin (Neuregulin 1) - NT-3 - NT-4 - PACAP
Neurons (also known as neurones and nerve cells) are electrically excitable cells in the nervous system that process and transmit information. In vertebrate animals, neurons are the core components of the brain, spinal cord and peripheral nerves.
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The term growth factor refers to a naturally occurring protein capable of stimulating cellular proliferation and cellular differentiation. Growth factors are important for regulating a variety of cellular processes.
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Exocytosis (ek-soh-sy-TOH-sis) is the process by which a cell directs secretory vesicles to the cell membrane. These membrane-bound vesicles contain soluble proteins to be secreted to the extracellular environment, as well as membrane proteins and lipids that are sent to become
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Apoptosis (pronounced ă-pŏp-tŏ’sĭs, apo tō' sis) is a form of programmed cell death in multicellular organisms. It is one of the main types of programmed cell death (PCD), and involves an orchestrated series of biochemical events leading to a
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The term progenitor cell is used in cell biology and developmental biology to refer to immature or undifferentiated cells, typically found in post-natal animals. While progenitor cells share many common features with stem cells, the term is far less restrictive.
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Nerve growth factor (NGF), is a small secreted protein which induces the differentiation and survival of particular target neurons (nerve cells). It is perhaps the prototypical growth factor, in that it is one of the first to be described - that work by Rita Levi-Montalcini
..... Click the link for more information.
Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor found in the brain and the periphery. It is a protein that acts on certain neurons of the central nervous system and the peripheral nervous system that helps to support the survival of existing neurons and encourage
..... Click the link for more information.
Neurotrophin-3, or NT-3 is a neurotrophic factor, in the NGF (Nerve Growth Factor)-family of neurotrophins. It is a protein growth factor which has activity on certain neurons of the peripheral and central nervous system; it helps to support the survival and differentiation of
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tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to a tyrosine residue in a protein. Tyrosine kinases are a subgroup of the larger class of protein kinases.
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Low Affinity Nerve Growth Factor Receptor (also called the LNGFR or p75 neurotrophin receptor) is one of the two receptor types for the neurotrophins, a family of protein growth factors which stimulate neuronal cells to survive and differentiate.
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Function

TrkA is the high affinity catalytic receptor for the neurotrophin, Nerve Growth Factor, or "NGF". As such, it mediates the multiple effects of NGF, which includes neuronal differentiation and survival.
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Function

TrkB is the high affinity catalytic receptor for several "neurotrophins", which are small protein growth factors that induce the survival and differentiation of distinct cell populations.
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TrkC is the high affinity catalytic receptor for the neurotrophin NT-3 (neurotrophin-3). As such, TrkC mediates the multiple effects of this neurotrophic factor, which includes neuronal differentiation and survival.
..... Click the link for more information.
Nerve growth factor (NGF), is a small secreted protein which induces the differentiation and survival of particular target neurons (nerve cells). It is perhaps the prototypical growth factor, in that it is one of the first to be described - that work by Rita Levi-Montalcini
..... Click the link for more information.
The term growth factor refers to a naturally occurring protein capable of stimulating cellular proliferation and cellular differentiation. Growth factors are important for regulating a variety of cellular processes.
..... Click the link for more information.
Proteins are large organic compounds made of amino acids arranged in a linear chain and joined together by peptide bonds between the carboxyl and amino groups of adjacent amino acid residues.
..... Click the link for more information.
Sensory neurons (neurones) are nerve cells within the nervous system responsible for converting external stimuli from the organism's environment into internal electrical motor reflex loops and several forms of involuntary behavior, including pain avoidance.
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Neurons (also known as neurones and nerve cells) are electrically excitable cells in the nervous system that process and transmit information. In vertebrate animals, neurons are the core components of the brain, spinal cord and peripheral nerves.
..... Click the link for more information.
Target cells are the sites where hormones act. Target cells are capable of responding to hormones because they bear receptors to which the hormone can bind. Hormones will float along the bloodstream until they find an appropriate target cell.
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Function

TrkA is the high affinity catalytic receptor for the neurotrophin, Nerve Growth Factor, or "NGF". As such, it mediates the multiple effects of NGF, which includes neuronal differentiation and survival.
..... Click the link for more information.
The soma, or perikaryon, is the bulbous end of a neuron, containing the cell nucleus. It is also known as the cell body. The word soma is Greek, meaning "body"; the soma of a neuron is often called the "cell body".
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axon or nerve fiber, is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma.

Anatomy


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The soma, or perikaryon, is the bulbous end of a neuron, containing the cell nucleus. It is also known as the cell body. The word soma is Greek, meaning "body"; the soma of a neuron is often called the "cell body".
..... Click the link for more information.
Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor found in the brain and the periphery. It is a protein that acts on certain neurons of the central nervous system and the peripheral nervous system that helps to support the survival of existing neurons and encourage
..... Click the link for more information.
Neurotrophins, also called "neurotrophic factors", are a family of protein which induce the survival of neurons. They belong to a family of growth factors, secreted proteins usually found in the blood stream which are capable of signaling particular cells to survive, differentiate,
..... Click the link for more information.
In animals, the brain or encephalon (Greek for "in the skull"), is the control center of the central nervous system, responsible for behavior. The brain is located in the head, protected by the skull and close to the primary sensory apparatus of vision, hearing,
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Proteins are large organic compounds made of amino acids arranged in a linear chain and joined together by peptide bonds between the carboxyl and amino groups of adjacent amino acid residues.
..... Click the link for more information.
Neurons (also known as neurones and nerve cells) are electrically excitable cells in the nervous system that process and transmit information. In vertebrate animals, neurons are the core components of the brain, spinal cord and peripheral nerves.
..... Click the link for more information.
The central nervous system (CNS) represents the largest part of the nervous system, including the brain and the spinal cord. Together with the peripheral nervous system, it has a fundamental role in the control of behavior.
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synapse. Synapses allow nerve cells to communicate with one another through axons and dendrites, converting electrical impulses into chemical signals.]]

Chemical synapses
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