
Ferroptosis contributes to multiple sclerosis and its pharmacological targeting suppresses experimental disease progression
- Author
- Emily Van San, Angela Debruyne (UGent) , Geraldine Veeckmans, Yulia Y. Y. Tyurina, Vladimir A. A. Tyurin, Hao Zheng, Sze Men Choi (UGent) , Koen Augustyns, Geert van Loo (UGent) , Bernhard Michalke, Vivek Venkataramani, Shinya Toyokuni, Huelya Bayir, Peter Vandenabeele (UGent) , Behrouz Hassannia (UGent) and Tom Vanden Berghe (UGent)
- Organization
- Project
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- Autophagy in inflammation and inflammatory disorders (ATLANTIS), from basic insights to experimental therapy
- Cell death activity regulation in inflammation and cancer
- Capacity building of a compound screening facility for Cuban-developed bioactive compounds targeting cell death and inflammation
- Cell Death Regulation and Role in Infection and Inflammatory Diseases
- Mechanisms of ferroptosis mediated immunoregulation
- MOlecular mechanisms of cellular DEath and Life decisions in Inflammation, Degeneration and Infection
- Factors that determine RIPK1-dependent necroptosis
- Unraveling the in vivo role of RIPK1: Physiological and pathological consequences of kinase-dependent and kinase-independent functions
- Investigating the role of ferroptosis in acute liver injury and multiple sclerosis with newly developed chemical tool compounds
- Thymic reprogramming: The role of Death Receptor 3 (DR3)
- Validation of ferroptosis-sensitizing combination therapies in patient-derived neuroblastoma models
- Nanoparticle-based ferroptosis-induction tot treat neuro-and glioblastoma
- Abstract
- 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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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-01HCZ0BJ8BFTA46W6NT4RNRYKE
- MLA
- Van San, Emily, et al. “Ferroptosis Contributes to Multiple Sclerosis and Its Pharmacological Targeting Suppresses Experimental Disease Progression.” CELL DEATH AND DIFFERENTIATION, vol. 30, no. 9, 2023, pp. 2092–103, doi:10.1038/s41418-023-01195-0.
- APA
- Van San, E., Debruyne, A., Veeckmans, G., Tyurina, Y. Y. Y., Tyurin, V. A. A., Zheng, H., … Vanden Berghe, T. (2023). Ferroptosis contributes to multiple sclerosis and its pharmacological targeting suppresses experimental disease progression. CELL DEATH AND DIFFERENTIATION, 30(9), 2092–2103. https://doi.org/10.1038/s41418-023-01195-0
- Chicago author-date
- Van San, Emily, Angela Debruyne, Geraldine Veeckmans, Yulia Y. Y. Tyurina, Vladimir A. A. Tyurin, Hao Zheng, Sze Men Choi, et al. 2023. “Ferroptosis Contributes to Multiple Sclerosis and Its Pharmacological Targeting Suppresses Experimental Disease Progression.” CELL DEATH AND DIFFERENTIATION 30 (9): 2092–2103. https://doi.org/10.1038/s41418-023-01195-0.
- Chicago author-date (all authors)
- Van San, Emily, Angela Debruyne, Geraldine Veeckmans, Yulia Y. Y. Tyurina, Vladimir A. A. Tyurin, Hao Zheng, Sze Men Choi, Koen Augustyns, Geert van Loo, Bernhard Michalke, Vivek Venkataramani, Shinya Toyokuni, Huelya Bayir, Peter Vandenabeele, Behrouz Hassannia, and Tom Vanden Berghe. 2023. “Ferroptosis Contributes to Multiple Sclerosis and Its Pharmacological Targeting Suppresses Experimental Disease Progression.” CELL DEATH AND DIFFERENTIATION 30 (9): 2092–2103. doi:10.1038/s41418-023-01195-0.
- Vancouver
- 1.Van San E, Debruyne A, Veeckmans G, Tyurina YYY, Tyurin VAA, Zheng H, et al. Ferroptosis contributes to multiple sclerosis and its pharmacological targeting suppresses experimental disease progression. CELL DEATH AND DIFFERENTIATION. 2023;30(9):2092–103.
- IEEE
- [1]E. Van San et al., “Ferroptosis contributes to multiple sclerosis and its pharmacological targeting suppresses experimental disease progression,” CELL DEATH AND DIFFERENTIATION, vol. 30, no. 9, pp. 2092–2103, 2023.
@article{01HCZ0BJ8BFTA46W6NT4RNRYKE, abstract = {{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.}}, author = {{Van San, Emily and Debruyne, Angela and Veeckmans, Geraldine and Tyurina, Yulia Y. Y. and Tyurin, Vladimir A. A. and Zheng, Hao and Choi, Sze Men and Augustyns, Koen and van Loo, Geert and Michalke, Bernhard and Venkataramani, Vivek and Toyokuni, Shinya and Bayir, Huelya and Vandenabeele, Peter and Hassannia, Behrouz and Vanden Berghe, Tom}}, issn = {{1350-9047}}, journal = {{CELL DEATH AND DIFFERENTIATION}}, language = {{eng}}, number = {{9}}, pages = {{2092--2103}}, title = {{Ferroptosis contributes to multiple sclerosis and its pharmacological targeting suppresses experimental disease progression}}, url = {{http://doi.org/10.1038/s41418-023-01195-0}}, volume = {{30}}, year = {{2023}}, }
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