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In the neuromuscular system, neurotrophic factors regulate motor neuron survival, function and synaptic connectivity, in part, through retrograde trafficking of activated neurotrophic factor-receptor complexes from the neuromuscular junction to the cell body. We recently demonstrated that brain-derived neurotrophic factor stimulation to muscles selectively enhances retrograde transport of signalling endosomes in fast, but not slow, motor neurons in vivo. Moreover, both axonal endosome transport and its brain-derived neurotrophic factor-mediated regulation are disrupted in mouse models of diseases impacting motor neurons, including amyotrophic lateral sclerosis and Charcot-Marie-Tooth disease. Here, we examined whether additional neurotrophic factors, when applied to distal axon terminals, share this transport-modulating property. Through imaging sciatic nerves in anaesthetised mice, we tracked the in vivo dynamics of signalling endosomes in fast and slow motor neurons via intramuscular injections of a fluorescent atoxic fragment of tetanus neurotoxin. These injections were co-administered with ciliary neurotrophic factor, hepatocyte growth factor, neurturin, or cleavage-resistant pro-brain-derived neurotrophic factor\u2014four growth factors with known effects on motor neurons. Compared to vehicle-treated controls, pro-brain-derived neurotrophic factor, hepatocyte growth factor and neurturin produced no detectable change in transport dynamics. In contrast, ciliary neurotrophic factor markedly reduced endosome speeds in both fast and slow motor neurons, indicating remarkable selectivity of specific neurotrophic factors in the regulation of signalling endosome transport in motor neurons. Understanding this selectivity may aid the development of muscle-targeted neurotrophic factor-based therapeutic strategies aimed at restoring axonal transport in neurodegenerative disease, peripheral neuropathy and nerve injury.<\/jats:p>","DOI":"10.1093\/braincomms\/fcag339","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T11:29:57Z","timestamp":1788521397000},"source":"Crossref","is-referenced-by-count":0,"title":["Ciliary neurotrophic factor slows axonal transport of signalling endosomes"],"prefix":"10.1093","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7103-5513","authenticated-orcid":false,"given":"Elena R","family":"Rhymes","sequence":"first","affiliation":[{"name":"Department of Neuromuscular Diseases and UCL Queen Square Motor Neuron Disease Centre, UCL Queen Square Institute of Neurology, University College London , London WC1N 3BG 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,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3782-9045","authenticated-orcid":false,"given":"James N","family":"Sleigh","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases and UCL Queen Square Motor Neuron Disease Centre, UCL Queen Square Institute of Neurology, University College London , London WC1N 3BG ,","place":["UK"]},{"name":"UK Dementia Research Institute, University College London , London WC1E 6BT ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7651-7442","authenticated-orcid":false,"given":"Andrew P","family":"Tosolini","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases and UCL Queen Square Motor Neuron Disease Centre, UCL Queen Square Institute of Neurology, University College London , London WC1N 3BG ,","place":["UK"]},{"name":"School of Biomedical Sciences, Faculty of Health, 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