Silencing Nogo-A promotes functional recovery in demyelinating disease.
Silencing Nogo-A promotes functional recovery in demyelinating disease.
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DOI：
10.1002/ana.21935
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发表时间：
2010-04
影响因子：
11.2
通讯作者：
Lovett-Racke, Amy E.
中科院分区：
文献类型：
--
作者：
Yang, Yuhong;Liu, Yue;Wei, Ping;Peng, Haiyan;Winger, Ryan;Hussain, Rehana Z.;Ben, Li-Hong;Cravens, Petra D.;Gocke, Anne R.;Puttaparthi, Krishna;Racke, Michael K.;McTigue, Dana M.;Lovett-Racke, Amy E.
确定抑制Nogo-A（一种轴突抑制蛋白）是否会促进多发性硬化（MS）小鼠模型的功能恢复。开发了特异性抑制Nogo-A的小干扰RNA（siRNA-NogoA）。通过免疫组织化学在体外和体内评估siRNA-NogoA沉默效果。在两种实验性自身免疫性脑脊髓炎（EAE）模型中静脉内施用siRNA。通过GAP 43的上调来测量轴突修复。采用ELISA、流式细胞术和~ 3 H-胸腺嘧啶核苷掺入法检测EAE小鼠髓鞘特异性T细胞的免疫学变化。SiRNA-NogoA在体外和体内抑制Nogo-A的表达。全身施用siRNA-NogoA改善了EAE并促进了轴突修复，如通过病变中增强的GAP 43+轴突所证明的。在siRNA-NogoA处理的小鼠中，髓鞘特异性T细胞增殖和细胞因子产生没有变化。沉默EAE中的Nogo-A促进功能恢复。治疗益处似乎是由轴突生长和修复介导的，并且不归因于髓鞘特异性T细胞的致脑炎能力的变化。沉默Nogo-A可能是MS患者预防由免疫介导的轴突损伤引起的永久性功能缺陷的治疗选择。
To determine if suppressing Nogo-A, an axonal inhibitory protein, will promote functional recovery in a murine model of multiple sclerosis (MS). A small interfering RNA was developed to specifically suppress Nogo-A (siRNA-NogoA). The siRNA-NogoA silencing effect was evaluated in vitro and in vivo via immunohistochemistry. The siRNA was administered intravenously in two models of experimental autoimmune encephalomyelitis (EAE). Axonal repair was measured by upregulation of GAP43. ELISA, flow cytometry and 3H-thymidine incorporation was used to determine immunological changes in myelin-specific T cells in mice with EAE. The siRNA-NogoA suppressed Nogo-A expression in vitro and in vivo. Systemic administration of siRNA-NogoA ameliorated EAE and promoted axonal repair as demonstrated by enhanced GAP43+ axons in the lesions. Myelin-specific T cell proliferation and cytokine production were unchanged in the siRNA-NogoA treated mice. Silencing Nogo-A in EAE promotes functional recovery. The therapeutic benefit appears to be mediated by axonal growth and repair, and is not attributable to changes in the encephalitogenic capacity of the myelin-specific T cells. Silencing Nogo-A may be a therapeutic option for MS patients to prevent permanent functional deficits caused by immune-mediated axonal damage.
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影响因子：
2.7
作者：
Braasch, DA;Paroo, Z;Corey, DR
通讯作者：
Corey, DR
影响因子：
2.5
作者：
Liu, HP;Ng, CEL;Tang, BL
通讯作者：
Tang, BL
DOI：
10.1097/01.wcb.0000040400.30600.af
发表时间：
2003-02-01
影响因子：
6.3
作者：
Wiessner, C;Bareyre, FM;Schwab, ME
通讯作者：
Schwab, ME
影响因子：
4.4
作者：
Gocke, Anne R.;Hussain, Rehana Z.;Racke, Michael K.
通讯作者：
Racke, Michael K.
影响因子：
158.5
作者：
Trapp, BD;Peterson, J;Bö, L
通讯作者：
Bö, L