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{{BioPsy}}
 
{{BioPsy}}
[[Image:Nerve Growth Factor (NGF).png|thumb|Nerve Growth Factor (NGF) (PDB code: 1bet) ([http://www.pdb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb68_1.html more details...])]]
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'''Nerve growth factor''' ('''NGF'''), is a small secreted [[protein]] which induces the [[Cellular differentiation|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]] and [[Stanley Cohen]] was rewarded with a [[Nobel Prize]].
'''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.
 
   
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While "nerve growth factor" refers to a single factor,<ref>{{MeshName|Nerve+Growth+Factor}}</ref> "nerve growth factors" refers to a family of factors also known as [[neurotrophin]]s.<ref>{{MeshName|Nerve+Growth+Factors}}</ref>
   
==Mechanism of action for NGF==
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==Function==
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NGF is critical for the survival and maintenance of [[Sympathetic nervous system|sympathetic]] and [[Sensory neuron|sensory]] [[neuron]]s.
   
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NGF is released from the [[target cell]]s, binds to and activates its high affinity receptor ([[TrkA]]), and is internalized into the responsive neuron. There are some data that show that NGF can be transported from the [[axon]] tip to [[soma (biology)|soma]], but it is unclear if this is necessary for effective [[cell signalling]]; in fact there are data showing that it is not. What is clear is that NGF binding and activation of TrkA is required for NGF-mediated neuronal survival and differentiation.
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==Receptor binding mechanism==
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{{main|Nerve growth factor receptor}}
 
NGF binds at least two receptors on the surface of cells which are capable of responding to this growth factor, [[TrkA]] (pronounced "Track A") and the [[LNGFR]] (for "[[low affinity nerve growth factor receptor]]").
 
NGF binds at least two receptors on the surface of cells which are capable of responding to this growth factor, [[TrkA]] (pronounced "Track A") and the [[LNGFR]] (for "[[low affinity nerve growth factor receptor]]").
   
===The TrkA Receptor===
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==History==
[[TrkA]] is a receptor tyrosine kinase (meaning it mediates its actions by causing the addition of phosphate molecules on certain tyrosines in the cell, activating cellular signaling). There are other related Trk receptors, [[TrkB]] and [[TrkC]]. Also, there are other neurotrophic factors structurally related to NGF: [[BDNF]] (for Brain Derived Neurotrophic Factor), [[NT-3]] (for [[Neurotrophin-3]]) and NT-4 (for Neurotrophin-4). While [[TrkA]] mediates the effects of NGF, [[TrkB]] binds and is activated by [[BDNF]], NT-4, and [[NT-3]], and [[TrkC]] binds and is activated only by [[NT-3]].
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[[Stanley Cohen (neurologist)|Stanley Cohen]] and [[Rita Levi-Montalcini]] won the 1986 [[Nobel Prize in Physiology or Medicine]] for their discovery of NGF and other growth factors.<ref>[http://nobelprize.org/medicine/laureates/1986/press.html The 1986 Nobel Prize in Physiology or Medicine for discoveries of growth factors]</ref><ref>Presentation Speech by Professor Kerstin Hall [http://nobelprize.org/medicine/laureates/1986/presentation-speech.html The Nobel Prize in Physiology or Medicine 1986]</ref><ref>[http://nobelprize.org/medicine/laureates/1986/levi-montalcini-lecture.html Rita Levi-Montalcini Nobel Lecture]</ref>
   
===The LNGFR===
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==Cultural and medical significance==
The other NGF receptor, the [[LNGFR]], (for [[Low affinity nerve growth factor receptor]],commonly known as [[p75]], plays a less clear role. LNGFR binds and serves as a "sink" for neurotrophins. Cells which express both the LNGFR and the Trk receptors might therefore have a greater activity - since they have a higher "microconcentration" of the neurotrophin. However, although NGF has been classically described as promoting neuron survival and differentiation, research performed in the early 2000's suggest that NGF with its prodomain attached (proNGF) can elicit apoptosis of cells that are positive for the [[LNGFR]] and negative for [[TrkA]]. [http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T0V-463KV3W-5&_coverDate=06%2F01%2F2002&_alid=344992322&_rdoc=1&_fmt=&_orig=search&_qd=1&_cdi=4872&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=9359772524bd9f280a4d2c0d79ee2fa1]
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In 2005, Italian scientists at [[University of Pavia]] found that a protein molecule known as the nerve growth factor (NGF) has high levels when people first fall in [[love]], but these levels return to as they were after one year. Specifically, four neurotrophin levels, i.e. NGF, BDNF, NT-3, and NT-4, of 58 subjects who had recently fallen in love were compared with levels in a control group who were either single or already engaged in a long-term relationship. The results showed that NGF levels were significantly higher in the subjects in love than as compared to either of the control groups.<ref>{{cite journal |author=Emanuele E, Politi P, Bianchi M, Minoretti P, Bertona M, Geroldi D |title=Raised plasma nerve growth factor levels associated with early-stage romantic love |journal=Psychoneuroendocrinology |volume=31 |issue=3 |pages=288–94 |year=2006 |pmid=16289361 |doi=10.1016/j.psyneuen.2005.09.002}} [http://dx.doi.org/10.1016/j.psyneuen.2005.09.002 link]</ref><ref>[http://www.redorbit.com/news/health/316141/molecule_gives_passionate_lovers_just_one_year/index.html "NGF" gives passionate lovers just one year], Reuters, November 29, 2005.</ref><ref>John Harris [http://education.guardian.co.uk/higher/research/story/0,9865,1653147,00.html Is love just a chemical?], Guardian, November 29, 2005.</ref>
   
Secreted proNGF has been demonstrated in a variety of neuronal and non-neuronal cell populations. It has been proposed that secreted proNGF can elicit [[neuron]] death in a variety of neurodegenerative conditions, including [[Alzheimers disease]], following the observation of an increase of proNGF in the [[nucleus (neuroanatomy)|nucleus]] basalis of postmortem Alzheimer's brains.
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It has also been tied to [[Alzheimer's disease]].<ref>{{cite journal |author=Counts S, Mufson E |title=The role of nerve growth factor receptors in cholinergic basal forebrain degeneration in prodromal Alzheimer disease |journal=J Neuropathol Exp Neurol |volume=64 |issue=4 |pages=263–72 |year=2005 |pmid=15835262}}</ref><ref>{{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}}</ref><ref>{{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}}</ref>
   
 
== See also ==
 
== See also ==
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* [[Amino acids]]
* [[Protein targeting]]
 
 
* [[Nervous System]]
 
* [[Nervous System]]
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* [[Neural development]]
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* [[Protein targeting]]
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* [[VGF|VGF Nerve Growth Factor-inducible]], a protein which expression is induced by NGF.
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==References==
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{{Reflist|2}}
   
 
==External links==
 
==External links==
* [http://nobelprize.org/medicine/laureates/1986/press.html The 1986 Nobel Prize in Physiology or Medicine for discoveries of growth factors]
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* {{MeshName|Nerve+Growth+Factor}}
* Presentation Speech by Professor Kerstin Hall [http://nobelprize.org/medicine/laureates/1986/presentation-speech.html The Nobel Prize in Physiology or Medicine 1986]
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* [http://keratos.free.fr/english/nervegrowthfactor.htm , NGF for corneal therapeutic purposes],
* [http://nobelprize.org/medicine/laureates/1986/levi-montalcini-lecture.html Rita Levi-Montalcini – Nobel Lecture]
 
* [http://www.biomedcentral.com/1471-2202/3/3 Nerve growth factor selectively regulates expression of transcripts encoding ribosomal proteins], BMC Neuroscience, February 2002.
 
* [http://dx.doi.org/10.1016/j.psyneuen.2005.09.002 Raised plasma nerve growth factor levels associated with early-stage romantic love], Psychoneuroendocrinology, November 2005.
 
* [http://www.redorbit.com/news/health/316141/molecule_gives_passionate_lovers_just_one_year/index.html "NGF" gives passionate lovers just one year], Reuters, November 29, 2005.
 
* John Harris [http://education.guardian.co.uk/higher/research/story/0,9865,1653147,00.html Is love just a chemical?], Guardian, November 29, 2005.
 
* CF Ibanez. Jekyll-Hyde neurotrophins: the story of proNGF. Trends Neurosci. 2002 Jun;25(6):284-6.
 
* SE Counts, EJ Mufson. The role of nerve growth factor receptors in cholinergic basal forebrain degeneration in prodromal Alzheimer disease.J Neuropathol Exp Neurol. 2005 Apr;64(4):263-72.
 
* [http://www.jcb.org/cgi/content/full/172/4/485a Active neuronal death]
 
*[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=16699811&query_hl=18&itool=pubmed_docsum] Neurotrophin signaling: many exciting surprises! Cell Mol Life Sci. 2006 May 15; [Epub ahead of print]
 
*[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=16472198&query_hl=18&itool=pubmed_docsum] Dissecting the diverse actions of pro- and mature neurotrophins. Curr Alzheimer Res. 2006 Feb;3(1):19-24.
 
*[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=16411894&query_hl=18&itool=pubmed_docsum] Clinical relevance of the neurotrophins and their receptors. Clin Sci (Lond). 2006 Feb;110(2):175-91.
 
   
 
{{Hormones}}
 
{{Hormones}}
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{{Nerve growth factor family}}
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{{Signaling proteins}}
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[[Category:Neurotrophins]]
 
[[Category:Neurotrophins]]
 
[[Category:Peptide hormones]]
 
[[Category:Peptide hormones]]
[[Category:Proteins]]
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[[Category:Growth factors]]
 
[[Category:Developmental neuroscience]]
 
[[Category:Developmental neuroscience]]
[[Category:Neurochemistry]]
 
   
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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 and Stanley Cohen was rewarded with a Nobel Prize.

While "nerve growth factor" refers to a single factor,[1] "nerve growth factors" refers to a family of factors also known as neurotrophins.[2]

FunctionEdit

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. There are some data that show that NGF can be transported from the axon tip to soma, but it is unclear if this is necessary for effective cell signalling; in fact there are data showing that it is not. What is clear is that NGF binding and activation of TrkA is required for NGF-mediated neuronal survival and differentiation.

Receptor binding mechanismEdit

Main article: Nerve growth factor receptor

NGF binds at least two receptors on the surface of cells which are capable of responding to this growth factor, TrkA (pronounced "Track A") and the LNGFR (for "low affinity nerve growth factor receptor").

HistoryEdit

Stanley Cohen and Rita Levi-Montalcini won the 1986 Nobel Prize in Physiology or Medicine for their discovery of NGF and other growth factors.[3][4][5]

Cultural and medical significanceEdit

In 2005, Italian scientists at University of Pavia found that a protein molecule known as the nerve growth factor (NGF) has high levels when people first fall in love, but these levels return to as they were after one year. Specifically, four neurotrophin levels, i.e. NGF, BDNF, NT-3, and NT-4, of 58 subjects who had recently fallen in love were compared with levels in a control group who were either single or already engaged in a long-term relationship. The results showed that NGF levels were significantly higher in the subjects in love than as compared to either of the control groups.[6][7][8]

It has also been tied to Alzheimer's disease.[9][10][11]

See also Edit

ReferencesEdit

  1. MeSH Nerve+Growth+Factor
  2. MeSH Nerve+Growth+Factors
  3. The 1986 Nobel Prize in Physiology or Medicine for discoveries of growth factors
  4. Presentation Speech by Professor Kerstin Hall The Nobel Prize in Physiology or Medicine 1986
  5. Rita Levi-Montalcini – Nobel Lecture
  6. Emanuele E, Politi P, Bianchi M, Minoretti P, Bertona M, Geroldi D (2006). Raised plasma nerve growth factor levels associated with early-stage romantic love. Psychoneuroendocrinology 31 (3): 288–94. link
  7. "NGF" gives passionate lovers just one year, Reuters, November 29, 2005.
  8. John Harris Is love just a chemical?, Guardian, November 29, 2005.
  9. Counts S, Mufson E (2005). The role of nerve growth factor receptors in cholinergic basal forebrain degeneration in prodromal Alzheimer disease. J Neuropathol Exp Neurol 64 (4): 263–72.
  10. Hempstead B (2006). Dissecting the diverse actions of pro- and mature neurotrophins. Curr Alzheimer Res 3 (1): 19–24.
  11. Allen S, Dawbarn D (2006). Clinical relevance of the neurotrophins and their receptors. Clin Sci (Lond) 110 (2): 175–91.

External linksEdit


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Target-derived NGF, BDNF, NT-3

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Template:Signaling proteins


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