Nerve growth factor (NGF) signaling via Tropomyosin receptor kinase A (TrkA) and p75 neurotrophin receptor (p75NTR) (NGF/TrkA/p75NTR)

The Nerve growth factor (NGF) signaling complex, involving the NGF ligand and its receptors Tropomyosin receptor kinase A (TrkA) and p75 neurotrophin receptor (p75NTR), is a fundamental pathway for the development and maintenance of sensory and sympathetic neurons (UniProt, 2024). NGF binds with high affinity to TrkA to promote cell survival and differentiation, while p75NTR can either facilitate these effects or independently trigger apoptosis (PubMed, PMID: 11485740). In adults, this signaling axis is a key mediator of pain, as NGF sensitizes nociceptors in response to injury or inflammation (StatPearls, 2023). Therapeutic targeting of this pathway includes anti-NGF monoclonal antibodies like Tanezumab for chronic pain and Trk inhibitors like Larotrectinib for cancers harboring NTRK gene fusions (NIH, 2021; FDA, 2018). However, clinical use is complicated by safety concerns such as rapidly progressive osteoarthritis for anti-NGF agents and neurological toxicities for Trk inhibitors (Nature Reviews Drug Discovery, 2021).

Other names

NGF-TrkA-p75NTR axisNeurotrophin signaling pathwayNGF/TrkA/p75 signalingNerve growth factor receptor signaling

The mechanism of action involves either the sequestration of the Nerve growth factor (NGF) ligand by monoclonal antibodies to prevent its binding to TrkA and p75NTR receptors, or the small-molecule inhibition of the Tropomyosin receptor kinase (Trk) intracellular tyrosine kinase domain to block downstream oncogenic and nociceptive signaling pathways.