Since it was first isolated by Nobel laureates Rita Levi-Montalcini and Stanley Cohen in 1954, numerous biological processes involving NGF have been identified, two of them being the survival of pancreatic beta cells and the regulation of the immune system.
The term nerve growth factor usually refers to the 2.5S, 26-kDa beta subunit of the protein, the only component of the 7S NGF complex that is biologically active (i.e. acting as a signaling molecule).
[5] However, several recent studies suggest that NGF is also involved in pathways besides those regulating the life cycle of neurons.
NGF can drive the expression of genes such as bcl-2 by binding to the Tropomyosin receptor kinase A, which stimulates the proliferation and survival of the target neuron.
Survival and PCD mechanisms are mediated through adaptor protein binding to the death domain of the p75NTR cytoplasmic tail.
In the process of inflammation, NGF is released in high concentrations by mast cells, and induces axonal outgrowth in nearby nociceptive neurons.
Studies suggest that NGF circulates throughout the entire body via the blood plasma, and is important for the overall maintenance of homeostasis.
In this pathway, recruitment of a guanine nucleotide exchange factor by the adaptor and docking proteins leads to activation of a membrane-associated G-protein known as Ras.
[7] Both Akt and RSK, components of the PI3K-Akt and MAPK pathways respectively, act to phosphorylate the cyclic AMP response element binding protein (CREB) transcription factor.
[7] Phosphorylated CREB translocates into the nucleus and mediates increased expression of anti-apoptotic proteins,[7] thus promoting NGF-mediated cell survival.
[7] Rita Levi-Montalcini and Stanley Cohen discovered NGF in the 1950s while faculty members at Washington University in St. Louis.
The critical discover was done by Levi-Montalcini and Hertha Meyer at the Carlos Chagas Filho Biophysics Institute of the Federal University of Rio de Janeiro in 1952.
[28] There is evidence of improved patient outcomes for several diseases of the nervous system, including acute intracerebral hemorrhage,[29] global developmental delay,[30] optic atrophy,[31] epilepsy [32] and cerebral palsy.
Recombinant human nerve growth factor (rhNGF; named cenegermin) has been formulated as an eye drop (0.002%).