000278040 001__ 278040 000278040 005__ 20250430100244.0 000278040 0247_ $$2doi$$a10.1016/j.nmd.2025.105345 000278040 0247_ $$2pmid$$apmid:40239532 000278040 0247_ $$2ISSN$$a0960-8966 000278040 0247_ $$2ISSN$$a1873-2364 000278040 037__ $$aDZNE-2025-00546 000278040 041__ $$aEnglish 000278040 082__ $$a610 000278040 1001_ $$0P:(DE-2719)9002065$$aYuan, Xidi$$b0$$eFirst author$$udzne 000278040 245__ $$aTherapeutic sphingosine-1-phosphate receptor modulation by repurposing fingolimod (FTY720) leads to mitigated neuropathy and improved clinical outcome in a mouse model for Charcot-Marie-Tooth 1X disease. 000278040 260__ $$aAmsterdam [u.a.]$$bElsevier Science$$c2025 000278040 3367_ $$2DRIVER$$aarticle 000278040 3367_ $$2DataCite$$aOutput Types/Journal article 000278040 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1745309704_8827 000278040 3367_ $$2BibTeX$$aARTICLE 000278040 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000278040 3367_ $$00$$2EndNote$$aJournal Article 000278040 520__ $$aPrevious studies have shown that both the innate and adaptive immune systems foster progression of neuropathy and clinical symptoms in a mouse model for Charcot-Marie-Tooth 1X disease. Here we demonstrate a possible therapeutic translation of these findings using the clinically approved sphingosine-1-phosphate receptor modulator fingolimod (FTY720) in connexin32-deficient mice mimicking Charcot-Marie-Tooth 1X disease. Treatment with FTY720 prevented an increase of CD8+ and CD4+ T-lymphocyte numbers in both femoral quadriceps nerve as well as in ventral spinal roots. While macrophages of ventral spinal roots show a similar, albeit non-significant trend, macrophages from quadriceps nerve are not reduced upon treatment. On the histopathological level, axonopathic changes were reduced in ventral spinal roots, but not in quadriceps nerves upon treatment. Electrophysiological recordings displayed improved nerve conduction parameters upon FTY720 treatment, while clinically, FTY720 treatment ameliorated distinct parameters of motor performance and grip strength. We suggest that targeting the adaptive immune system might be a pharmacological treatment option for mitigating disease burden particularly in severe cases of Charcot-Marie-Tooth 1X. 000278040 536__ $$0G:(DE-HGF)POF4-352$$a352 - Disease Mechanisms (POF4-352)$$cPOF4-352$$fPOF IV$$x0 000278040 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de 000278040 650_7 $$2Other$$aAxon damage 000278040 650_7 $$2Other$$aFTY720 000278040 650_7 $$2Other$$aFingolimod 000278040 650_7 $$2Other$$aInherited peripheral neuropathy 000278040 650_7 $$2Other$$aMacrophages 000278040 650_7 $$2Other$$aMyelin 000278040 650_7 $$2Other$$aNeuroinflammation 000278040 650_7 $$2Other$$aT-lymphocytes 000278040 7001_ $$aKlein, Dennis$$b1 000278040 7001_ $$aMaier, Anna-Maria$$b2 000278040 7001_ $$aMartini, Rudolf$$b3 000278040 773__ $$0PERI:(DE-600)2008287-3$$a10.1016/j.nmd.2025.105345$$gVol. 50, p. 105345 -$$p105345$$tNeuromuscular disorders$$v50$$x0960-8966$$y2025 000278040 8564_ $$uhttps://pub.dzne.de/record/278040/files/DZNE-2025-00546.pdf$$yOpenAccess 000278040 8564_ $$uhttps://pub.dzne.de/record/278040/files/DZNE-2025-00546.pdf?subformat=pdfa$$xpdfa$$yOpenAccess 000278040 909CO $$ooai:pub.dzne.de:278040$$popenaire$$popen_access$$pVDB$$pdriver$$pdnbdelivery 000278040 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)9002065$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b0$$kDZNE 000278040 9131_ $$0G:(DE-HGF)POF4-352$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vDisease Mechanisms$$x0 000278040 9141_ $$y2025 000278040 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2024-12-05 000278040 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2024-12-05 000278040 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search$$d2024-12-05 000278040 915__ $$0LIC:(DE-HGF)CCBYNCND4$$2HGFVOC$$aCreative Commons Attribution-NonCommercial-NoDerivs CC BY-NC-ND 4.0 000278040 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bNEUROMUSCULAR DISORD : 2022$$d2024-12-05 000278040 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences$$d2024-12-05 000278040 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2024-12-05 000278040 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2024-12-05 000278040 915__ $$0StatID:(DE-HGF)9900$$2StatID$$aIF < 5$$d2024-12-05 000278040 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess 000278040 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC$$d2024-12-05 000278040 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2024-12-05 000278040 915__ $$0StatID:(DE-HGF)0420$$2StatID$$aNationallizenz$$d2024-12-05$$wger 000278040 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2024-12-05 000278040 9201_ $$0I:(DE-2719)1110011$$kAG Neher (München)$$lNeuroimmunology and Neurodegenerative Disease$$x0 000278040 980__ $$ajournal 000278040 980__ $$aVDB 000278040 980__ $$aUNRESTRICTED 000278040 980__ $$aI:(DE-2719)1110011 000278040 9801_ $$aFullTexts