Details

Autor(en) / Beteiligte

• Van San, Emily
• Debruyne, Angela C
• Veeckmans, Geraldine
• Tyurina, Yulia Y
• Tyurin, Vladimir A
• Zheng, Hao
• Choi, Sze Men
• Augustyns, Koen
• van Loo, Geert
• Michalke, Bernhard
• Venkataramani, Vivek
• Toyokuni, Shinya
• Bayir, Hülya
• Vandenabeele, Peter
• Hassannia, Behrouz
• Vanden Berghe, Tom

Titel

Ferroptosis contributes to multiple sclerosis and its pharmacological targeting suppresses experimental disease progression

Ist Teil von

• Cell death and differentiation, 2023-09, Vol.30 (9), p.2092-2103

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2023

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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.