Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS), with a putative autoimmune origin and complex pathogenesis. Modification of the natural history of MS by reducing relapses and slowing disability accumulation was first attained in the 1990 s with the development of the first-generation disease-modifying therapies. Glatiramer acetate (GA), a copolymer of L-alanine, L-lysine, L-glutamic acid, and L-tyrosine, was discovered due to its ability to suppress the animal model of MS, experimental autoimmune encephalomyelitis. Extensive clinical trials and long-term assessments established the efficacy and the safety of GA. Furthermore, studies of the therapeutic processes induced by GA in animal models and in MS patients indicate that GA affects various levels of the innate and the adaptive immune response, generating deviation from proinflammatory to anti-inflammatory pathways. This includes competition for binding to antigen presenting cells; driving dendritic cells, monocytes, and B-cells toward anti-inflammatory responses; and stimulating T-helper 2 and T-regulatory cells. The immune cells stimulated by GA reach the CNS and secrete in situ anti-inflammatory cytokines alleviating the pathological processes. Furthermore, cumulative findings reveal that in addition to its immunomodulatory effect, GA promotes neuroprotective repair processes such as neurotrophic factors secretion, remyelination, and neurogenesis. This review aims to provide an overview of MS pathology diagnosis and treatment as well as the diverse mechanism of action of GA.

中文翻译：

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醋酸格拉替雷治疗多发性硬化症：从第一代疗法到阐明免疫调节和修复


多发性硬化症 （MS） 是一种中枢神经系统 （CNS） 的慢性炎症性脱髓鞘和神经退行性疾病，具有推定的自身免疫起源和复杂的发病机制。通过减少复发和减缓残疾积累来改变 MS 的自然病程是在 1990 年代随着第一代疾病修饰疗法的开发而首次实现的。醋酸格拉替雷 （GA） 是 L-丙氨酸、L-赖氨酸、L-谷氨酸和 L-酪氨酸的共聚物，因其能够抑制 MS（实验性自身免疫性脑脊髓炎）动物模型而被发现。广泛的临床试验和长期评估确定了 GA 的有效性和安全性。此外，对动物模型和 MS 患者中 GA 诱导的治疗过程的研究表明，GA 影响不同水平的先天性和适应性免疫反应，导致从促炎途径到抗炎途径的偏差。这包括与抗原呈递细胞结合的竞争;驱动树突状细胞、单核细胞和 B 细胞走向抗炎反应;以及刺激 T 辅助细胞 2 和 T 调节细胞。受 GA 刺激的免疫细胞到达 CNS 并原位分泌抗炎细胞因子，缓解病理过程。此外，累积研究结果表明，除了免疫调节作用外，GA 还促进神经保护性修复过程，例如神经营养因子的分泌、髓鞘再生和神经发生。本综述旨在概述 MS 病理学诊断和治疗以及 GA 的各种作用机制。