Tropomyosin receptor kinase A and p75 neurotrophin receptor (TrkA/p75NTR)

The TrkA/p75NTR neurotrophin receptor system is a dual-receptor complex composed of the high-affinity tropomyosin receptor kinase A (TrkA) and the p75 neurotrophin receptor (p75NTR), which together coordinate the cellular response to nerve growth factor (NGF) (NIH, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4570488/). TrkA is a receptor tyrosine kinase that, upon NGF binding, activates intracellular cascades such as the PI3K/Akt and MAPK/ERK pathways to promote neuronal survival, differentiation, and neurite outgrowth (PatSnap, https://patsnap.com). The p75NTR, a member of the tumor necrosis factor receptor superfamily, acts as a co-receptor that increases the affinity and specificity of TrkA for NGF, but it can also signal independently to trigger apoptosis or growth cone collapse, particularly when activated by pro-neurotrophins (Wikipedia, https://en.wikipedia.org/wiki/P75_neurotrophin_receptor). This receptor system is a significant therapeutic target in oncology, where NTRK1 gene fusions act as oncogenic drivers, and in chronic pain management, where NGF-mediated signaling contributes to peripheral and central sensitization (NIH, https://pubmed.ncbi.nlm.nih.gov/26372482/). Drugs targeting this system include selective TrkA inhibitors like larotrectinib and entrectinib for cancer, and anti-NGF monoclonal antibodies like tanezumab for chronic pain (NIH, https://pubmed.ncbi.nlm.nih.gov/31112321/). However, therapeutic intervention must balance clinical benefits against safety concerns, such as neurological side effects for kinase inhibitors and rapidly progressive osteoarthritis for anti-NGF therapies (NIH, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4254551/).

Other names

NTRK1NGFRCD271High-affinity nerve growth factor receptorLow-affinity nerve growth factor receptorp75 neurotrophin receptorTropomyosin receptor kinase ALNGFRTrkA

Inhibition of TrkA tyrosine kinase activity; Sequestration of NGF to prevent receptor binding; Modulation of p75NTR-mediated apoptotic or survival signaling.