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| 100 | 1 | _ | |a Kohle, Felix |0 P:(DE-HGF)0 |b 0 |e Corresponding author |
| 245 | _ | _ | |a Kinesin-5 inhibition improves neural regeneration in experimental autoimmune neuritis |
| 260 | _ | _ | |a London |c 2023 |b BioMed Central |
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| 520 | _ | _ | |a AbstractBackground Autoimmune neuropathies can result in long-term disability and incomplete recovery, despite adequatefirst-line therapy. Kinesin-5 inhibition was shown to accelerate neurite outgrowth in different preclinical studies.Here, we evaluated the potential neuro-regenerative effects of the small molecule kinesin-5 inhibitor monastrol in arodent model of acute autoimmune neuropathies, experimental autoimmune neuritis.Methods Experimental autoimmune neuritis was induced in Lewis rats with the neurogenic P2-peptide. At thebeginning of the recovery phase at day 18, the animals were treated with 1 mg/kg monastrol or sham and observeduntil day 30 post-immunisation. Electrophysiological and histological analysis for markers of inflammation and remyelinationof the sciatic nerve were performed. Neuromuscular junctions of the tibialis anterior muscles were analysedfor reinnervation. We further treated human induced pluripotent stem cells-derived secondary motor neurons withmonastrol in different concentrations and performed a neurite outgrowth assay.Results Treatment with monastrol enhanced functional and histological recovery in experimental autoimmuneneuritis. Motor nerve conduction velocity at day 30 in the treated animals was comparable to pre-neuritis values.Monastrol-treated animals showed partially reinnervated or intact neuromuscular junctions. A significant and dosedependentaccelerated neurite outgrowth was observed after kinesin-5 inhibition as a possible mode of action.Conclusion Pharmacological kinesin-5 inhibition improves the functional outcome in experimental autoimmuneneuritis through accelerated motor neurite outgrowth and histological recovery. This approach could be of interest toimprove the outcome of autoimmune neuropathy patients.Keywords Experimental autoimmune neuritis, Guillain–Barré syndrome, Autoimmune neuropathy, Eg5, Monastrol,Neuroregeneration |
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| 536 | _ | _ | |a DFG project 491454339 - Open-Access-Publikationskosten / 2022 – 2024 / Universität zu Köln und Uniklinik Köln (491454339) |0 G:(GEPRIS)491454339 |c 491454339 |x 1 |
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| 700 | 1 | _ | |a Ackfeld, Robin |0 P:(DE-HGF)0 |b 1 |
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| 700 | 1 | _ | |a Klein, Ines |0 P:(DE-HGF)0 |b 3 |
| 700 | 1 | _ | |a Svačina, Martin K. R. |0 P:(DE-HGF)0 |b 4 |
| 700 | 1 | _ | |a Schneider, Christian |b 5 |
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| 700 | 1 | _ | |a Barham, Mohammed |0 P:(DE-HGF)0 |b 7 |
| 700 | 1 | _ | |a Vilchez, David |0 P:(DE-HGF)0 |b 8 |
| 700 | 1 | _ | |a Lehmann, Helmar C. |0 P:(DE-HGF)0 |b 9 |
| 773 | _ | _ | |a 10.1186/s12974-023-02822-w |g Vol. 20, no. 1, p. 139 |0 PERI:(DE-600)2156455-3 |n 1 |p 139 |t Journal of neuroinflammation |v 20 |y 2023 |x 1742-2094 |
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