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

Nerve growth factor (NGF) is a neurotrophic protein essential for the development, survival, and maintenance of sensory and sympathetic neurons [1.3.4, 1.3.5]. It signals through two primary receptors: the high-affinity tropomyosin receptor kinase A (TrkA) and the low-affinity p75 neurotrophin receptor (p75NTR) [1.1.4, 1.2.2]. In adults, the NGF-TrkA axis is a critical mediator of pain, as NGF is upregulated in response to injury and inflammation, leading to the sensitization of nociceptors and the upregulation of pain-related neurotransmitters like substance P [1.1.4, 1.3.3]. This pathway has become a major therapeutic target for chronic pain conditions, including osteoarthritis and chronic low back pain, primarily through the development of anti-NGF monoclonal antibodies [1.5.1, 1.5.3]. Beyond pain, dysregulation of NGF signaling is implicated in neurodegenerative diseases like Alzheimer's and various cancers where NTRK gene fusions act as oncogenic drivers [1.3.4, 1.5.2]. However, clinical development of anti-NGF therapies has been complicated by significant safety concerns, most notably the risk of rapidly progressive osteoarthritis (RPOA) [1.1.2, 1.1.5].

Other names

Beta-nerve growth factorNeurotrophic receptor tyrosine kinase type 1p75 neurotrophin receptorNTRK1NGFRCD271p140TrkTrkA

Monoclonal antibodies bind to and neutralize circulating NGF, preventing its interaction with TrkA and p75NTR receptors [1.3.1, 1.5.2]. Small molecule inhibitors competitively bind to the ATP-binding site of the Trk kinase domain to block downstream signaling [1.3.1, 1.5.4].