Neurotrophin receptor (NTR)

Neurotrophin receptors are a family of cell surface receptors that mediate the biological effects of neurotrophins, such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), which are critical for the development and maintenance of the nervous system (Huang & Reichardt, 2003, PMID: 12932330). This family is divided into two main classes: the tropomyosin receptor kinases (TrkA, TrkB, and TrkC) and the p75 neurotrophin receptor (p75NTR) (Bothwell, 1995, PMID: 7670306). Trk receptors are high-affinity tyrosine kinases that activate intracellular signaling cascades, including the PI3K/Akt and MAPK pathways, to promote neuronal survival, differentiation, and synaptic plasticity (Kaplan & Miller, 2000, PMID: 10906341). In contrast, p75NTR is a member of the tumor necrosis factor receptor superfamily and can either facilitate Trk signaling or independently trigger apoptosis depending on the presence of specific ligands and co-receptors (Roux & Barker, 2002, PMID: 12185850). In clinical medicine, neurotrophin receptors have gained significant prominence as therapeutic targets, particularly in oncology, where chromosomal rearrangements involving the NTRK genes lead to oncogenic Trk fusion proteins (Amatu et al., 2019, PMID: 30832334). This discovery led to the development of pan-Trk inhibitors like larotrectinib and entrectinib, which are approved as histology-agnostic therapies for patients with NTRK fusion-positive cancers (Drilon et al., 2018, PMID: 29466156). Beyond cancer, these receptors are being explored as targets for neurodegenerative conditions like Alzheimer's disease and for the management of chronic pain (Mantyh et al., 2011, PMID: 21441497).

Other names

Neurotrophic receptorTrk receptorTropomyosin receptor kinaseNeurotrophic receptor tyrosine kinaseNTRKp75 neurotrophin receptorp75NTRLow-affinity nerve growth factor receptor

Inhibition of the intracellular tyrosine kinase domain of tropomyosin receptor kinases (TrkA, TrkB, and TrkC) to block downstream oncogenic signaling pathways in cells harboring NTRK gene fusions.