{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNeurotrophin‐3 (NTF3) is a key factor in orchestrating neural development and regeneration. It regulates early morphogenetic events such as tooth formation and directs the differentiation and survival of distinct neuronal lineages. For example, NTF3 expression in developing dental tissues and in the spinal cord provides trophic support that promotes corticospinal axon regeneration after injury. In addition, muscle–derived NTF3 helps specify proprioceptive sensory neurons and supports inner ear innervation, while structural studies reveal that NTF3 binds its cognate receptor (p75NTR) in a symmetric 2:2 complex—a configuration that appears to be essential for its proper signaling—and transcriptional regulation via factors like POU3F2 further modulates neuronal differentiation and cell‐fate decisions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn cancer and inflammatory settings NTF3 emerges as a multifunctional modulator. In melanoma and metastatic breast cancer cells, NTF3 can stimulate cell migration, re‐epithelialization and suppress cytotoxic immune responses—mechanisms that favor tumor growth and survival (for instance, by promoting anoikis resistance in suspended breast cancer cells). In neuroblastoma cells, NTF3 contributes to cell survival by counteracting dependence receptor–induced apoptosis, a feature that may offer a therapeutic target. Moreover, NTF3 is produced by inflammatory cells (such as eosinophils) in allergic conditions, and evidence in disorders like mastocytosis suggests that augmented NTF3 signaling can affect both mast cell survival and paracrine interactions within the tumor microenvironment."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "23"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its canonical neurotrophic role, NTF3 is increasingly recognized as a mediator of neuroplastic and systemic processes. Altered NTF3 expression is associated with several neuropsychiatric and neurodegenerative disorders. Studies report that fluctuating NTF3 levels accompany state‐dependent changes in major depression, bipolar disorder and attention‐deficit/hyperactivity disorder, while genetic polymorphisms in NTF3 have been linked to schizophrenia and eating disorders. In Alzheimer’s disease models, dysregulated NTF3 levels correlate with amyloid pathology, and NTF3 also contributes to skeletal repair by acting as an osteogenic and angiogenic factor. Interestingly, NTF3 produced by bronchial smooth muscle cells and adipocytes plays roles in regulating airway inflammation and sympathetic innervation, thereby influencing energy expenditure and obesity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "24", "end_ref": "43"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Irina Nosrat, Ake Seiger, Lars Olson, et al. 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