Neurotrophin signaling pathway (NT signaling) (NT signaling)

Neurotrophin-related signaling encompasses the biochemical cascades initiated by the neurotrophin family of growth factors, including Nerve Growth Factor (NGF), Brain-Derived Neurotrophic Factor (BDNF), Neurotrophin-3 (NT-3), and Neurotrophin-4 (NT-4) [PMID: 12757305]. These ligands interact with two distinct classes of cell surface receptors: the high-affinity Tropomyosin receptor kinases (TrkA, TrkB, and TrkC) and the low-affinity p75 neurotrophin receptor (p75NTR) [PMID: 11485749]. Activation of Trk receptors typically triggers the PI3K/Akt, Ras/MAPK, and PLC-gamma pathways, which are essential for neuronal survival, differentiation, and synaptic plasticity [PMID: 15582415]. In contrast, p75NTR can mediate diverse outcomes, including apoptosis or axonal growth, depending on its association with various co-receptors [PMID: 12846976]. Dysregulation of neurotrophin signaling is a hallmark of several pathologies; for instance, NTRK gene fusions act as oncogenic drivers in various cancers, while reduced BDNF signaling is implicated in neurodegenerative and psychiatric disorders [PMID: 24913304, PMID: 30333316]. Therapeutic interventions include Trk inhibitors like larotrectinib for fusion-positive cancers and anti-NGF antibodies like tanezumab for chronic pain management [PMID: 29466156, PMID: 30623160].

Other names

Neurotrophin-mediated signalingTrk receptor signalingNeurotrophic factor signaling

Drugs targeting this pathway primarily act by inhibiting the kinase activity of Tropomyosin receptor kinases (TrkA/B/C), sequestering neurotrophin ligands like Nerve Growth Factor (NGF) to prevent receptor binding, or acting as agonists to mimic neurotrophic effects.