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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)
Verlagsversion DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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
Korrespondenzautor
Schlagwörter Experimental Autoimmune Encephalomyelitis; Lipid-peroxidation; Cell-death; B-cells; Iron; Myelin; Mice; Induction; Injury; Damage
ISSN (print) / ISBN 1350-9047
e-ISSN 1476-5403
Zeitschrift Cell Death and Differentiation
Quellenangaben Band: 30, Heft: 9, Seiten: 2092-2103 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Verlagsort Campus, 4 Crinan St, London, N1 9xw, England
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Analytical BioGeoChemistry (BGC)
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