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.
NGF is released from the target cells, binds to and activates its high affinity receptor (TrkA), and is internalized into the responsive neuron. There is some data that shows 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 is 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.
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.
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 Alzheimer's disease, following the observation of an increase of proNGF in the nucleus basalis of postmortem Alzheimer's brains.
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