Neurotrophic factor signaling pathway (NTF pathway) (NTF pathway)

The neurotrophic factor signaling pathways are a complex network of intracellular cascades initiated by the binding of neurotrophins—including Nerve Growth Factor (NGF), Brain-Derived Neurotrophic Factor (BDNF), Neurotrophin-3 (NT-3), and Neurotrophin-4 (NT-4)—to their respective receptors (Huang & Reichardt, 2001, PMID: 11520902). These pathways primarily utilize two types of receptors: the high-affinity Tropomyosin receptor kinases (TrkA, TrkB, and TrkC) and the low-affinity p75 neurotrophin receptor (p75NTR), which together regulate neuronal survival, differentiation, and synaptic plasticity (Park & Poo, 2013, PMID: 23303723). In the central nervous system, these pathways are vital for cognitive function and memory, and their dysregulation is linked to neurodegenerative conditions such as Alzheimer's disease and psychiatric disorders like depression (NIH, 2023). In oncology, chromosomal rearrangements leading to NTRK gene fusions result in constitutive activation of these pathways, driving various solid tumors (NCI, 2024). Consequently, these pathways are targeted by Trk inhibitors like Larotrectinib and Entrectinib for cancer treatment, while research continues into neurotrophin mimetics for treating neurological decline (PubChem, 2024). Therapeutic modulation also includes the sequestration of NGF by monoclonal antibodies to treat chronic pain, although this approach has faced safety challenges (StatPearls, 2023).

Other names

Neurotrophin signaling pathwayNT signalingNeurotrophic factor cascadeGrowth factor pathways in the nervous system

Modulation of neurotrophic signaling through Tropomyosin receptor kinase (Trk) inhibition in oncology or through the use of neurotrophin mimetics and Nerve Growth Factor (NGF) sequestration in neurology and pain management.