Nerve Growth Factor (NGF)
The first discovered neurotrophic factor (Nobel Prize 1986), essential for survival and maintenance of sensory and sympathetic neurons. NGF deficiency contributes to neurodegenerative conditions. Trofinetide, while not directly targeting NGF, is an IGF-1-derived tripeptide approved for the neurodevelopmental disorder Rett syndrome.
Technical Context
NGF (120 amino acids as the mature form) was discovered by Rita Levi-Montalcini and Stanley Cohen (Nobel Prize 1986). NGF binds TrkA (high affinity, promoting survival, differentiation, and axon growth of sensory and sympathetic neurons) and p75NTR (lower affinity, context-dependent effects). NGF is produced by target tissues innervated by NGF-dependent neurons — providing retrograde trophic support (neurons that successfully connect to target tissues survive; those that don't undergo apoptosis during development). In adults, NGF maintains sensory neuron function and is upregulated during inflammation and tissue injury (contributing to inflammatory pain/hyperalgesia — anti-NGF antibodies are in development for chronic pain). Trofinetide (GPE = Gly-Pro-Glu, the N-terminal tripeptide of IGF-1) acts through a different mechanism: it modulates neuroinflammation, glial function, and synaptic signalling through pathways that are not yet fully characterised, but early evidence suggests involvement of NF-κB and glutamate signalling modulation.