Neurotrophic factor signaling pathways (NTF signaling)

Neurotrophic factor signaling pathways are essential regulatory networks that govern the growth, survival, and functional maintenance of neurons in the central and peripheral nervous systems [11, 12]. These pathways are activated by a family of secreted proteins known as neurotrophic factors (NTFs), including neurotrophins (NGF, BDNF, NT-3, NT-4), the GDNF family, and neuropoietic cytokines [1, 11]. Signaling is primarily mediated through high-affinity receptor tyrosine kinases (TrkA, TrkB, TrkC) and the p75 neurotrophin receptor (p75NTR), which trigger downstream cascades such as the PI3K/Akt, MAPK/ERK, and PLCγ pathways [4, 5, 13]. Dysregulation of these signals is implicated in the pathogenesis of neurodegenerative diseases like Alzheimer's and Parkinson's, as well as psychiatric disorders such as depression [3, 8, 10]. Pharmacological interventions target these pathways through various mechanisms: Trk receptor agonists (e.g., 7,8-DHF) aim to provide neuroprotection, while anti-NGF antibodies (e.g., tanezumab) are used for chronic pain management [1, 6]. Additionally, Trk inhibitors (e.g., larotrectinib) are approved for treating cancers harboring TRK gene fusions [13]. Therapeutic challenges include achieving effective blood-brain barrier penetration and managing pleiotropic side effects resulting from the broad biological roles of these factors [1, 4].

Other names

Neurotrophin signaling pathwayNTF signalingBDNF-TrkB signalingNGF-TrkA signalingGDNF-RET signalingNeurotrophic factor signaling

Modulation of neurotrophic factor levels or receptor activity, including Trk receptor agonism for neuroprotection, Trk inhibition for oncology, and NGF sequestration for analgesia.