Nerve Growth Factor (NGF): The Neurotrophin That Keeps Nerves Alive

Nerve growth factor (NGF) holds a special place in biology: it was the first neurotrophin ever discovered, and the work that revealed it earned a Nobel Prize. More than a historical curiosity, NGF remains a molecule of real clinical consequence — it is the active principle of an approved eye-drop medicine and a major, complicated target in the science of pain.

What NGF is

NGF is a small secreted protein (a neurotrophin) that neurons and the tissues they supply use to communicate survival signals. Its defining role, established in classic experiments, is trophic support: developing and mature sensory and sympathetic neurons depend on NGF supplied by their target tissues to survive, grow, and stay functional. Take the NGF away, and those neurons wither; supply it, and they thrive and extend their fibers.

This is the core idea of the neurotrophic hypothesis — that target tissues release limited amounts of neurotrophins, and neurons compete for them, with those that get enough surviving and those that don't being pruned. NGF was the founding example.

How NGF signals

NGF acts through two receptors:

• TrkA (NTRK1) — the high-affinity receptor tyrosine kinase that mediates NGF's classic survival and growth signals, activating pathways such as PI3K/Akt (survival) and MAPK/ERK (growth and differentiation).
• p75NTR — a lower-affinity receptor shared across neurotrophins that modulates the response and, in some contexts, can promote the opposite (cell death) signal, sharpening specificity.

The balance of TrkA and p75 signaling shapes whether NGF tells a neuron to grow, survive, or, in certain settings, die back.

NGF at the body's surfaces: the cornea

One tissue especially dependent on NGF is the cornea, the clear front of the eye, which is among the most densely innervated surfaces in the body. Corneal nerves both provide sensation and deliver trophic signals that keep the surface healthy and able to heal. When those nerves are damaged — by herpes eye infection, diabetes, surgery, or chemical injury — the cornea loses this support and can stop healing, a condition called neurotrophic keratitis.

This is where NGF became a drug. Cenegermin (Oxervate) is recombinant human NGF formulated as an eye drop; by restoring NGF directly to the ocular surface it supports corneal nerves and epithelial cells and promotes genuine healing — treating the root cause rather than only lubricating the eye. It is the first approved topical neurotrophin therapy.

The pain paradox

NGF is not only protective. In adults, NGF is also a powerful pain mediator: it sensitizes nociceptors (pain-sensing nerve endings) and is released in injured and inflamed tissue, amplifying pain signaling. This gives NGF a genuinely double-edged character — essential for keeping certain neurons alive, yet a driver of chronic pain when overactive.

That paradox has shaped drug development in opposite directions. Supplying NGF helps a tissue like the cornea that has lost its nerve support. Blocking NGF — with anti-NGF antibodies such as tanezumab — has been pursued to relieve chronic pain conditions like osteoarthritis, where it can be strongly analgesic, though this approach has faced safety questions around joints. The same molecule is thus both a therapy to give and a target to block, depending on the disease.

NGF among the neurotrophins

NGF is the prototype of a family that also includes BDNF (brain-derived neurotrophic factor), NT-3, and NT-4. They share the job of supporting neuronal survival and plasticity but differ in which neurons they favor and which Trk receptors they prefer (BDNF signals mainly through TrkB). Studying NGF opened the entire field of neurotrophic signaling and its relevance to development, regeneration, and disease.

Key takeaways

• Nerve growth factor was the first neurotrophin discovered and is essential for the survival and growth of sensory and sympathetic neurons.
• It signals through the high-affinity TrkA receptor (survival and growth) and the lower-affinity p75 receptor (modulation).
• The cornea depends heavily on NGF; losing corneal nerve support causes neurotrophic keratitis, treated by the recombinant-NGF eye drop cenegermin.
• NGF is double-edged: protective as a trophic factor but also a driver of pain, which is why both giving NGF and blocking it are therapeutic strategies in different diseases.
• NGF is the founding member of the neurotrophin family that includes BDNF.

This article is educational and does not constitute medical advice.