Van San, E.* ; Debruyne, A.C.* ; Veeckmans, G.* ; Tyurina, Y.Y.* ; Tyurin, V.A.* ; Zheng, H.* ; Choi, S.M.* ; Augustyns, K.* ; van Loo, G.* ; Michalke, B. ; Venkataramani, V.* ; Toyokuni, S.* ; Bayir, H.* ; Vandenabeele, P.* ; Hassannia, B.* ; Vanden Berghe, T.*
     
 
    
        
Ferroptosis contributes to multiple sclerosis and its pharmacological targeting suppresses experimental disease progression.
    
    
        
    
    
        
        Cell Death Differ. 30, 2092-2103 (2023)
    
    
    
		
		
			
				Multiple sclerosis (MS) is a chronic autoimmune disorder characterized by central nervous (CNS) demyelination resulting in axonal injury and neurological deficits. Essentially, MS is driven by an auto-amplifying mechanism of inflammation and cell death. Current therapies mainly focus on disease modification by immunosuppression, while no treatment specifically focuses on controlling cell death injury. Here, we report that ferroptosis, an iron-catalyzed mode of regulated cell death (RCD), contributes to MS disease progression. Active and chronic MS lesions and cerebrospinal fluid (CSF) of MS patients revealed several signs of ferroptosis, reflected by the presence of elevated levels of (labile) iron, peroxidized phospholipids and lipid degradation products. Treatment with our candidate lead ferroptosis inhibitor, UAMC-3203, strongly delays relapse and ameliorates disease progression in a preclinical model of relapsing-remitting MS. In conclusion, the results identify ferroptosis as a detrimental and targetable factor in MS. These findings create novel treatment options for MS patients, along with current immunosuppressive strategies.
			
			
				
			
		 
		
			
				
					
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        Publikationstyp
        Artikel: Journalartikel
    
 
    
        Dokumenttyp
        Wissenschaftlicher Artikel
    
 
    
        Typ der Hochschulschrift
        
    
 
    
        Herausgeber
        
    
    
        Schlagwörter
        Experimental Autoimmune Encephalomyelitis; Lipid-peroxidation; Cell-death; B-cells; Iron; Myelin; Mice; Induction; Injury; Damage
    
 
    
        Keywords plus
        
    
 
    
    
        Sprache
        englisch
    
 
    
        Veröffentlichungsjahr
        2023
    
 
    
        Prepublished im Jahr 
        0
    
 
    
        HGF-Berichtsjahr
        2023
    
 
    
    
        ISSN (print) / ISBN
        1350-9047
    
 
    
        e-ISSN
        1476-5403
    
 
    
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	    Band: 30,  
	    Heft: 9,  
	    Seiten: 2092-2103 
	    Artikelnummer: ,  
	    Supplement: ,  
	
    
 
  
        
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            Verlag
            Nature Publishing Group
        
 
        
            Verlagsort
            Campus, 4 Crinan St, London, N1 9xw, England
        
 
	
        
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            0000-00-00
        
 
        
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        Begutachtungsstatus
        Peer reviewed
    
 
     
    
        POF Topic(s)
        30202 - Environmental Health
    
 
    
        Forschungsfeld(er)
        Environmental Sciences
    
 
    
        PSP-Element(e)
        G-504800-002
    
 
    
        Förderungen
        Excellence of Science MODEL-IDI
CD-INFLADIS
~Consortium of excellence at University of Antwerp INFLA-MED
Industrial Research Fund
BOF-IMPULS from University of Antwerp
Research Foundation Flanders
Foundation against cancer
Charcot Foundation
VLIRUOS
FWO
Flemish Institute of Biotechnology VIB
iBOF ATLANTIS
CRIG
GIGG consortia
NIH
    
 
    
        Copyright
        
    
 	
    
    
    
    
    
        Erfassungsdatum
        2023-10-06