补体系统
视神经脊髓炎
实验性自身免疫性脑脊髓炎
免疫学
水通道蛋白4
炎症
医学
替代补体途径
补体C1q
少突胶质细胞
髓鞘少突胶质细胞糖蛋白
视神经炎
神经保护
多发性硬化
免疫系统
中枢神经系统
生物
神经科学
髓鞘
病理
作者
Xu Li,Huiming Xu,Siqi Chen,Wei Jiang,Shabbir Khan Afridi,Yuge Wang,Xin Ren,Yipeng Zhao,Shuiqing Lai,Xiusheng Qiu,Yu‐Wen Alvin Huang,Yifu Cui,Hui Yang,Wei Qiu,Changyong Tang
标识
DOI:10.1016/j.ymthe.2023.07.017
摘要
Neuromyelitis optica (NMO) is an autoimmune inflammatory disease of the central nervous system (CNS) characterized by transverse myelitis and optic neuritis. The pathogenic serum IgG antibody against the aquaporin-4 (AQP4) on astrocytes triggers the activation of the complement cascade, causing astrocyte injury, followed by oligodendrocyte injury, demyelination, and neuronal loss. Complement C3 is positioned as a central player that relays upstream initiation signals to activate downstream effectors, potentially stimulating and amplifying host immune and inflammatory responses. However, whether targeting the inhibition of C3 signaling could ameliorate tissue injury, locomotor defects, and visual impairments in NMO remains to be investigated. In this study, using the targeted C3 inhibitor CR2-Crry led to a significant decrease in complement deposition and demyelination in both slice cultures and focal intracerebral injection models. Moreover, the treatment downregulated the expression of inflammatory cytokines and improved motor dysfunction in a systemic NMO mouse model. Similarly, employing serotype 2/9 adeno-associated virus (AAV2/9) to induce permanent expression of CR2-Crry resulted in a reduction in visual dysfunction by attenuating NMO-like lesions. Our findings reveal the therapeutic value of inhibiting the complement C3 signaling pathway in NMO.
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