Ferroptosis contributes to multiple sclerosis and its pharmacological targeting suppresses experimental disease progression.
Ferroptosis contributes to multiple sclerosis and its pharmacological targeting suppresses experimental disease progression.
复制标题
DOI：
10.1038/s41418-023-01195-0
复制
发表时间：
2023-09
影响因子：
12.4
通讯作者：
Vanden Berghe, Tom
中科院分区：
文献类型：
--
作者：
Van San, Emily;Debruyne, Angela C. C.;Veeckmans, Geraldine;Tyurina, Yulia Y. Y.;Tyurin, Vladimir A. A.;Zheng, Hao;Choi, Sze Men;Augustyns, Koen;van Loo, Geert;Michalke, Bernhard;Venkataramani, Vivek;Toyokuni, Shinya;Bayir, Huelya;Vandenabeele, Peter;Hassannia, Behrouz;Vanden Berghe, Tom
多发性硬化症（MS）是一种以中枢神经（CNS）脱髓鞘为特征的慢性自身免疫性疾病，可导致轴突损伤和神经功能缺损。本质上，多发性硬化症是由炎症和细胞死亡的自动放大机制驱动的。目前的治疗方法主要是通过免疫抑制来改变疾病，而没有专门的治疗方法来控制细胞死亡损伤。在这里，我们报道铁凋亡，一种铁催化的调节细胞死亡（RCD）模式，有助于MS疾病的进展。活跃性和慢性多发性硬化症病变和多发性硬化症患者的脑脊液（CSF）显示出一些铁下垂的迹象，反映在（不稳定的）铁、过氧化磷脂和脂质降解产物水平升高。我们的候选铁下垂先导抑制剂UAMC-3203在复发-缓解型MS的临床前模型中显著延迟复发和改善疾病进展。总之，研究结果确定铁下垂是MS的有害和可靶向因素。这些发现为MS患者提供了新的治疗选择，以及目前的免疫抑制策略。
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.
登录
查看更多内容
影响因子：
14.8
作者：
Kagan VE;Mao G;Qu F;Angeli JP;Doll S;Croix CS;Dar HH;Liu B;Tyurin VA;Ritov VB;Kapralov AA;Amoscato AA;Jiang J;Anthonymuthu T;Mohammadyani D;Yang Q;Proneth B;Klein-Seetharaman J;Watkins S;Bahar I;Greenberger J;Mallampalli RK;Stockwell BR;Tyurina YY;Conrad M;Bayır H
通讯作者：
Bayır H
影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
影响因子：
5.3
作者：
Jhelum, Priya;Santos-Nogueira, Eva;David, Samuel
通讯作者：
David, Samuel
影响因子：
25
作者：
Dong, Yifei;D'Mello, Charlotte;Yong, V. Wee
通讯作者：
Yong, V. Wee
影响因子：
5.6
作者：
Kennedy, Peter G. E.;George, Woro;Yu, Xiaoli
通讯作者：
Yu, Xiaoli