% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@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},
}