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首页> 外文期刊>Clinical immunology: The official journal of the Clinical Immunology Society >Fumaric acid and its esters: An emerging treatment for multiple sclerosis with antioxidative mechanism of action
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Fumaric acid and its esters: An emerging treatment for multiple sclerosis with antioxidative mechanism of action

机译：富马酸及其酯类：具有抗氧化作用机制的多发性硬化症的新兴治疗方法

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Fumaric acid was originally therapeutically used in psoriasis. Several lines of evidence have demonstrated immunomodulatory but also neuroprotective effects for FAE. Clinical studies in psoriasis showed a reduction of peripheral CD4+ and CD8+ T-lymphocytes due to the ability of FAE to induce apoptosis. In vitro studies with the ester dimethylfumarate (DMF) described an inhibitory effect on nuclear factor kappa B (NF-κB)-dependent transcription of tumor necrosis factor-alpha (TNF-α) induced genes in human endothelial cells. Animal experiments in the mouse model of central nervous system demyelination, MOG-induced experimental autoimmune encephalomyelitis, revealed a clear preservation of myelin and axonal density in the plaque. Molecular studies showed that this is based on the antioxidative mechanism of action via induction of the transcription factor Nrf-2. A phase II clinical trial in relapsing-remitting multiple sclerosis (RRMS) patients with dimethylfumarate showed a significant reduction in the number of gadolinium enhancing lesions after 24. weeks.
机译：富马酸最初在牛皮癣中用于治疗。几条证据已证明对FAE具有免疫调节作用和神经保护作用。银屑病的临床研究表明，由于FAE诱导凋亡的能力，外周CD4 +和CD8 + T淋巴细胞减少。富马酸二甲酯（DMF）的体外研究描述了对人内皮细胞中肿瘤坏死因子-α（TNF-α）诱导的基因的核因子κB（NF-κB）依赖性转录的抑制作用。在MOG诱导的实验性自身免疫性脑脊髓炎的中枢神经系统脱髓鞘小鼠模型中进行的动物实验显示，斑块中髓磷脂和轴突密度得到了清晰的保存。分子研究表明，这是基于通过诱导转录因子Nrf-2产生的抗氧化作用机理。富马酸二甲酯的复发缓解型多发性硬化症（RRMS）患者的II期临床试验显示，在24周后，enhancing增强病变的数量显着减少。

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