Nerve growth factor
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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.
Mechanism of action for NGF
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
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.The LNGFR
The other NGF receptor, the LNGFR (for Low affinity nerve growth factor receptor, plays a somewhat less clear role. Some researchers have shown that the 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. [link]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 basalis of postmortem Alzheimer's brains.
See also
External links
- [The 1986 Nobel Prize in Physiology or Medicine for discoveries of growth factors]
- Presentation Speech by Professor Kerstin Hall [The Nobel Prize in Physiology or Medicine 1986]
- [Rita Levi-Montalcini – Nobel Lecture]
- [Nerve growth factor selectively regulates expression of transcripts encoding ribosomal proteins], BMC Neuroscience, February 2002.
- [Raised plasma nerve growth factor levels associated with early-stage romantic love], Psychoneuroendocrinology, November 2005.
- ["NGF" gives passionate lovers just one year], Reuters, November 29, 2005.
- John Harris [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.
- [Active neuronal death]
- [link] Neurotrophin signaling: many exciting surprises! Cell Mol Life Sci. 2006 May 15; [Epub ahead of print]
- [link] Dissecting the diverse actions of pro- and mature neurotrophins. Curr Alzheimer Res. 2006 Feb;3(1):19-24.
- [link] Clinical relevance of the neurotrophins and their receptors. Clin Sci (Lond). 2006 Feb;110(2):175-91.
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