Neurotrophin 1061573 223420516 2008-07-04T00:16:33Z Correogsk 4595831 '''Neurotrophins''' are a family of proteins that induce the survival of [[neurons]]. They belong to a class of [[growth factors]], [[exocytosis|secreted]] proteins, which are capable of signaling particular cells to survive, differentiate, or grow. 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 [[apoptosis|programmed cell death]] - thus allowing the neurons to survive. Neurotrophins also induce differentiation of [[progenitor cells]], to form neurons. Some scientists employ the term "neurotrophin" as a synonym for "neurotrophic factor", 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, p75 and the "Trk" family of [[Tyrosine kinase]]s receptors. * p75 is a [[low affinity neurotrophin receptor]], to which all neurotrophins bind. It is a member of the tumour necrosis super family. * 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. * NGF binds to TrkA, BDNF and NT-4 bind to TrkB and NT-3 binds to [[TrkC]]. In addition NT-3 also binds to and activates TrkA and TrkB but it does so less efficiently. * Whilst the Trk receptors have a clearly defined trophic role, p75 receptors activate signalling pathways which can also result in [[apoptosis]]. ==Nerve growth factor== {{Main|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 neuron|sensory]] [[neuron]]s. NGF is released from the [[target cell]]s, 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 [[Soma (biology)|cell body]]. This movement of NGF from [[axon]] tip to [[soma (biology)|soma]] is thought to be involved in the long-distance signaling of neurons{{Fact|date=May 2007}}. ==Brain-derived neurotrophic factor== {{Main|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 [[neuron]]s 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 [[synapse]]s through [[axonal]] and dendritic sprouting. In the brain, it is active in the [[hippocampus]], [[Cerebral cortex|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 [[mammal]]ian brain are formed prenatally, parts of the adult brain retain the ability to grow new neurons from neural [[stem cell]]s; 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. ==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" ({{Gene|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. The terminology has become confusing since most scientists use the term "neurotrophin" to refer only to NGF, BDNF, NT-3 and NT-4, while a few scientists use the term "neurotrophin" to refer to any neurotrophic factor, of which there are many. 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|STAT3]]. It has been implicated in the induction of [[interleukin-1|IL-1]] (via induction of [[corticosterone]] and [[interleukin-6|IL-6]]) and [[serum amyloid A]], and in [[B cell]] [[hyperplasia]]. This cytokine is capable of B cell activation via gp130 receptor stimulation.<ref>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</ref> ==Neurotrophin-3== {{Main|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 [[neuron]]s 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 [[synapse]]s. [[NT-3]] was the third neurotrophic factor to be characterized, after NGF and BDNF. Although the vast majority of neurons in the [[mammal]]ian brain are formed prenatally, parts of the adult brain retain the ability to grow new neurons from neural [[stem cell]]s; 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== {{main|NT-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.<ref name="nt4">{{Cite web|url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=retrieve&dopt=default&list_uids=4909&rn=1|title=Entrez database entry for NT-4/5|accessdate = 2007-05-07|publisher=NCBI}}</ref> ==References== {{reflist}} * {{cite journal |author=Arévalo J, Wu S |title=Neurotrophin signaling: many exciting surprises! |journal=Cell Mol Life Sci |volume=63 |issue=13 |pages=1523–37 |year=2006 |pmid=16699811 |doi=10.1007/s00018-006-6010-1}} * {{cite journal |author=Hempstead B |title=Dissecting the diverse actions of pro- and mature neurotrophins |journal=Curr Alzheimer Res |volume=3 |issue=1 |pages=19–24 |year=2006 |pmid=16472198 |doi=10.2174/156720506775697061}} * {{cite journal |author=Allen S, Dawbarn D |title=Clinical relevance of the neurotrophins and their receptors |journal=Clin Sci (Lond) |volume=110 |issue=2 |pages=175–91 |year=2006 |pmid=16411894}} ==External links== * [http://7e.devbio.com/article.php?ch=13&id=143 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]]) * [http://www.drkoop.com/newsdetail/93/533621.html Dr.Koop.com] - 'New Clues to Neurological Diseases Discovered: Findings could lead to new treatments, two studies suggest', Steven Reinberg, ''[[HealthDay]]'' ([[July 5]], [[2006]]) * [http://ethesis.helsinki.fi/julkaisut/laa/biola/vk/wartiovaara/review.html Helsinki.fi] - 'Neurotrophic factors' * {{MeshName|Neurotrophins}} {{Neurotrophins}} [[Category:Neurochemistry]] [[Category:Neurotrophins|*]] [[Category:Programmed cell death]] [[de:Neurotrophin]] [[es:neurotrofina]] [[nl:Neurotrofine]]