Nerve growth factor receptor (NGFR)

Nerve growth factor receptors are a group of cell surface proteins that bind Nerve Growth Factor (NGF) to regulate the development, survival, and maintenance of neurons [6, 11]. This group primarily consists of the high-affinity Tropomyosin receptor kinase A (TrkA, encoded by NTRK1) and the low-affinity p75 neurotrophin receptor (p75NTR, encoded by NGFR) [3, 13, 15]. TrkA is a receptor tyrosine kinase that initiates signaling cascades like Ras/MAPK and PI3K/Akt to promote neuronal growth and survival, while p75NTR, a member of the TNF receptor superfamily, acts as a co-receptor or independent signaling unit that can mediate apoptosis or refine survival signals depending on the cellular context [5, 7, 10]. In disease, TrkA is frequently involved in oncogenic gene fusions that drive various solid tumors and is a key mediator of chronic and inflammatory pain signaling [4, 8, 18]. Therapeutic strategies targeting these receptors include the use of Trk-specific tyrosine kinase inhibitors, such as larotrectinib, for NTRK-fusion-positive cancers, and anti-NGF monoclonal antibodies like tanezumab to inhibit pain by preventing receptor activation [16, 18, 20]. However, the clinical development of anti-NGF therapies has faced significant hurdles due to safety concerns, particularly a risk of rapidly progressive osteoarthritis [19, 20].

Other names

p75 neurotrophin receptorp75NTRCD271Tropomyosin receptor kinase ATrkANTRK1Low-affinity nerve growth factor receptorHigh-affinity nerve growth factor receptorTNFRSF16Gp80-LNGFRNeurotrophic tyrosine kinase receptor type 1

Monoclonal antibodies sequester the NGF ligand to prevent receptor binding; receptor tyrosine kinase inhibitors block the intracellular kinase activity of TrkA; and small molecule modulators can allosterically regulate p75NTR signaling pathways.