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@ARTICLE{Kohle:1025358,
      author       = {Kohle, Felix and Ackfeld, Robin and Hommen, Franziska and
                      Klein, Ines and Svačina, Martin K. R. and Schneider,
                      Christian and Fink, Gereon R. and Barham, Mohammed and
                      Vilchez, David and Lehmann, Helmar C.},
      title        = {{K}inesin-5 inhibition improves neural regeneration in
                      experimental autoimmune neuritis},
      journal      = {Journal of neuroinflammation},
      volume       = {20},
      number       = {1},
      issn         = {1742-2094},
      address      = {London},
      publisher    = {BioMed Central},
      reportid     = {FZJ-2024-02821},
      pages        = {139},
      year         = {2023},
      abstract     = {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},
      cin          = {INM-3},
      ddc          = {610},
      cid          = {I:(DE-Juel1)INM-3-20090406},
      pnm          = {5251 - Multilevel Brain Organization and Variability
                      (POF4-525) / DFG project 491454339 -
                      Open-Access-Publikationskosten / 2022 – 2024 /
                      Universität zu Köln und Uniklinik Köln (491454339)},
      pid          = {G:(DE-HGF)POF4-5251 / G:(GEPRIS)491454339},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {37296476},
      UT           = {WOS:001002907500001},
      doi          = {10.1186/s12974-023-02822-w},
      url          = {https://juser.fz-juelich.de/record/1025358},
}