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Neurotrophins are a family of proteins that induce the survival,[1] development and function[2] of neurons.

They belong to a class of growth factors, secreted proteins, which are capable of signaling particular cells to survive, differentiate, or grow.[3] Growth factors such as neurotrophins that promote the survival of neurons are known as neurotrophic factors. 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.

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. Neurotrophins are chemicals that help to stimulate and control neurogenesis.

Contents

Terminology

Some scientists employ the term "neurotrophin" as a synonym for "neurotrophic factor",[4] while most reserve the term "neurotrophin" for four structurally related factors: nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4).

Another neurotrophic factor, known as novel neurotrophin-1 (NNT1) is structurally unrelated to NGF, BDNF, NT-3 and NT-4.

Receptors

There are two classes of receptors for neurotrophins: p75 and the "Trk" family of Tyrosine kinases receptors.[5]

Types

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Nerve growth factor

Nerve growth factor (NGF), the prototypical growth factor, is a protein secreted by a neuron's target cell. 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 on the neuron, and is internalized into the responsive neuron. The NGF/TrkA complex is subsequently trafficked back to the neuron's cell body. This movement of NGF from axon tip to soma is thought to be involved in the long-distance signaling of neurons.

NGF levels have been shown to be significantly elevated during the first year of a romantic relationship.

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.

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 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.

Novel Neurotrophin-1

Novel Neurotrophin-1 (NNT-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. The term "neurotrophin" is commonly used to refer collectively to the four structurally related factors NGF, BDNF, NT-3 and NT-4, while NNT1 bears no structural resemblance to these four proteins.

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.[6]

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.

NT-3 is unique among the neurotrophins 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). Mice born without the ability to make NT-3 have loss of proprioceptive and subsets of mechanoreceptive sensory neurons.

Neurotrophin-4

Neurotrophin-4 (NT-4) 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.[7]

References

  1. ^ Hempstead BL (February 2006). "Dissecting the diverse actions of pro- and mature neurotrophins". Curr Alzheimer Res 3 (1): 19–24. doi:10.2174/156720506775697061. PMID 16472198. http://www.bentham-direct.org/pages/content.php?CAR/2006/00000003/00000001/005AT.SGM.  
  2. ^ Reichardt LF (September 2006). "Neurotrophin-regulated signalling pathways". Philos. Trans. R. Soc. Lond., B, Biol. Sci. 361 (1473): 1545–64. doi:10.1098/rstb.2006.1894. PMID 16939974. PMC 1664664. http://journals.royalsociety.org/openurl.asp?genre=article&id=doi:10.1098/rstb.2006.1894.  
  3. ^ Allen SJ, Dawbarn D (February 2006). "Clinical relevance of the neurotrophins and their receptors". Clin. Sci. 110 (2): 175–91. doi:10.1042/CS20050161. PMID 16411894. http://www.clinsci.org/cs/110/0175/cs1100175.htm.  
  4. ^ MeSH Neurotrophins
  5. ^ Arévalo JC, Wu SH (July 2006). "Neurotrophin signaling: many exciting surprises!". Cell. Mol. Life Sci. 63 (13): 1523–37. doi:10.1007/s00018-006-6010-1. PMID 16699811.  
  6. ^ 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
  7. ^ "Entrez database entry for NT-4/5". NCBI. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=retrieve&dopt=default&list_uids=4909&rn=1. Retrieved 2007-05-07.  

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

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