Utility of experimental animal models of myasthenia gravis for the elucidation of pathogenic mechanisms and development of new medications.
Utility of experimental animal models of myasthenia gravis for the elucidation of pathogenic mechanisms and development of new medications.
复制标题
重症肌无力实验动物模型用于阐明致病机制和开发新药物。
DOI：
10.1111/cen3.12517
复制
发表时间：
2019
影响因子：
--
通讯作者：
Shigemoto K.
中科院分区：
文献类型：
--
作者：
Mori S;Shigemoto K.
重症肌无力 (MG) 是一种以眼睑下垂、疲劳和肌肉无力为特征的自身免疫性疾病，由致病性自身抗体与神经肌肉接头处的突触后膜蛋白相关引起。尽管在 MG 患者的血清中发现了多种自身抗体，但大多数抗体与 MG 之间的因果关系尚未得到证实。用重症肌无力实验动物模型建立候选抗体的致病性是必不可少的。针对乙酰胆碱受体和肌肉特异性激酶的自身抗体的致病性已通过使用纯化抗原进行主动免疫或通过 MG 患者自身抗体的被动转移得到证实。此外，MG动物模型不仅显示了MG患者中观察到的肌肉无力和萎缩表现的致病机制，还显示了新疗法的功效和治疗药物的不良反应。在这里，我们回顾了动物 MG 模型对阐明 MG 致病机制和开发该疾病药物的贡献。
Myasthenia gravis (MG) is an autoimmune disease characterized by ptosis, fatigue and muscle weakness, caused by the association of pathogenic autoantibodies with postsynaptic membrane proteins at neuromuscular junctions. Although various autoantibodies have been found in sera from patients with MG, causal relationships with MG have not been shown for most antibodies. Establishment of the pathogenicity of candidate antibodies with experimental animal models of myasthenia gravis is indispensable. The pathogenicity of autoantibodies against acetylcholine receptors and muscle‐specific kinase has been confirmed by active immunization with purified antigens or by passive transfer of autoantibodies from patients with MG. Furthermore, animal models of MG have shown not only the pathogenic mechanisms underlying the manifestation of muscle weakness and atrophy observed in patients with MG, but also the efficacy of novel therapies and the adverse effects of therapeutic drugs. Here, we review the contributions of animal MG models to the elucidation of the pathogenic mechanisms of MG and the development of medications for the disease.