Re-Examining the Role of TNF in MS Pathogenesis and Therapy.
Re-Examining the Role of TNF in MS Pathogenesis and Therapy.
复制标题
重新审视肿瘤坏死因子在多发性硬化症发病和治疗中的作用。
DOI：
10.3390/cells9102290
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发表时间：
2020-10-14
期刊：
影响因子：
6
通讯作者：
Gentile A
中科院分区：
文献类型：
--
作者：
Fresegna D;Bullitta S;Musella A;Rizzo FR;De Vito F;Guadalupi L;Caioli S;Balletta S;Sanna K;Dolcetti E;Vanni V;Bruno A;Buttari F;Stampanoni Bassi M;Mandolesi G;Centonze D;Gentile A
多发性硬化症 (MS) 是一种常见的自身免疫性神经系统疾病。临床和实验研究描述了疾病过程中特定细胞因子的异常表达。肿瘤坏死因子 (TNF) 是一种已被证明在多发性硬化症中发挥关键作用的主要细胞因子。 TNF是一种多效细胞因子，调节免疫系统和中枢神经系统（CNS）的许多生理和病理功能。来自人类和实验性多发性硬化症研究的令人信服的证据表明，TNF 与多发性硬化症的各种病理特征有关，包括免疫失调、脱髓鞘、突触病和神经炎症。然而，由于 TNF 信号传导的复杂性，包括两种配体（可溶性和跨膜 TNF）和两种受体，即 TNF 受体 1 型 (TNFR1) 和 2 型 (TNFR2)，并且由于其细胞和环境表达差异，在 MS 中靶向 TNF 系统是一个持续的挑战。本综述总结了 TNF 在多发性硬化症和不同多发性硬化症动物模型中病理生理学作用的证据，特别关注旨在控制这种神经系统疾病中失调的 TNF 信号传导的药物治疗。
Multiple sclerosis (MS) is a common neurological disorder of putative autoimmune origin. Clinical and experimental studies delineate abnormal expression of specific cytokines over the course of the disease. One major cytokine that has been shown to play a pivotal role in MS is tumor necrosis factor (TNF). TNF is a pleiotropic cytokine regulating many physiological and pathological functions of both the immune system and the central nervous system (CNS). Convincing evidence from studies in human and experimental MS have demonstrated the involvement of TNF in various pathological hallmarks of MS, including immune dysregulation, demyelination, synaptopathy and neuroinflammation. However, due to the complexity of TNF signaling, which includes two-ligands (soluble and transmembrane TNF) and two receptors, namely TNF receptor type-1 (TNFR1) and type-2 (TNFR2), and due to its cell- and context-differential expression, targeting the TNF system in MS is an ongoing challenge. This review summarizes the evidence on the pathophysiological role of TNF in MS and in different MS animal models, with a special focus on pharmacological treatment aimed at controlling the dysregulated TNF signaling in this neurological disorder.