Nerve growth factor and its receptors (TrkA and p75NTR) (NGF/TrkA/p75NTR)

Nerve growth factor (NGF) is a neurotrophic factor essential for the development, maintenance, and survival of sensory and sympathetic neurons. It exerts its biological effects by binding to two distinct receptors: the high-affinity tropomyosin receptor kinase A (TrkA) and the low-affinity p75 neurotrophin receptor (p75NTR). In adults, NGF is a critical mediator of pain, where its upregulation in inflamed or injured tissues sensitizes nociceptors and contributes to chronic pain states such as osteoarthritis and chronic back pain. Beyond the nervous system, NGF signaling is involved in wound healing, immune regulation, and the progression of certain cancers, particularly those harboring NTRK gene fusions. Therapeutic strategies include monoclonal antibodies that neutralize NGF to provide analgesia, small molecule inhibitors that target the TrkA kinase domain for oncology, and recombinant NGF for treating neurotrophic keratitis. However, the clinical use of systemic anti-NGF therapies has been complicated by significant safety concerns, most notably rapidly progressive osteoarthritis.

Other names

Beta-nerve growth factorNGFBHSAN5Tropomyosin receptor kinase A (TrkA)NTRK1p75 neurotrophin receptor (p75NTR)NGFRLow-affinity nerve growth factor receptor (LNGFR)CD271

Monoclonal antibodies (e.g., Tanezumab) sequester and neutralize circulating NGF to prevent its binding to TrkA and p75NTR receptors, thereby inhibiting pain signaling. Small molecule inhibitors (e.g., Larotrectinib) block the intracellular kinase activity of TrkA to inhibit oncogenic signaling in NTRK-fusion positive cancers. Recombinant human NGF (Cenegermin) acts as an agonist to promote corneal healing and neuronal survival.