Nerve growth factor

Overview
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.

Function
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 mechanism
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").

TrkA, B, and C receptors
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), and there are other neurotrophic factors structurally related to NGF (BDNF, NT-3, and NT-4)


 * TrkA mediates the effects of NGF
 * TrkB binds and is activated by BDNF, NT-4, and NT-3
 * TrkC binds and is activated only by NT-3

LNGFR receptor
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.

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.

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

Cultural significance
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.

It has also been tied to Alzheimer's disease.