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

(2023) CELL DEATH AND DIFFERENTIATION. 30(9). p.2092-2103
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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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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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