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Nat Com:细胞穿透肽能将治疗蛋白送进大脑

摘要 : 很多治疗药物如果能够穿过血脑屏障(BBB)到达它们作用点的话,将具有有效治疗中枢神经系统疾病的潜力。本期Nature Communications报告了一种新的输送工具,它能克服这一屏障,并有可能帮助治疗多发性硬化(MS)。

 很多治疗药物如果能够穿过血脑屏障(BBB)到达它们作用点的话,将具有有效治疗中枢神经系统疾病的潜力。本期Nature Communications报告了一种新的输送工具,它能克服这一屏障,并有可能帮助治疗多发性硬化(MS)。BBB使得有毒物质、感染性物质和其他有潜在危险性的物质无法进入大脑,但它也会阻断治疗药物,对阻断蛋白质等大分子尤为有效。

Je-Min Choi及同事通过使用属于一类细胞穿透肽(它们能够穿过细胞膜在细胞内运输蛋白或药物)的一种工具绕过了这一问题。迄今为止,这些肽中没有一种曾被用来高效穿过BBB,但该研究小组新设计的dNP2肽能够做到这一点。当注射了附着到荧光蛋白上的dNP2时,实验鼠的脊髓和大脑变得发荧光,显示dNP2-蛋白复合物成功穿过了BBB。

作者然后将dNP2附着到CTLA4 (抑制淋巴细胞激活的一种蛋白)的一个片段上。淋巴细胞的过度激活、导致脑组织和脊髓组织损伤是MS病的病因。在MS病的一个小鼠模型中,dNP2-CTLA4治疗有效提高了健康状况。这些结果表明,dNP2在用基于蛋白的治疗药物帮助治疗包括MS在内的神经疾病方面可能会被证明有效。

原文链接:

dNP2 is a blood–brain barrier-permeable peptide enabling ctCTLA-4 protein delivery to ameliorate experimental autoimmune encephalomyelitis

原文摘要:

Central nervous system (CNS)-infiltrating effector T cells play critical roles in the development and progression of multiple sclerosis (MS). However, current drugs for MS are very limited due to the difficulty of delivering drugs into the CNS. Here we identify a cell-permeable peptide, dNP2, which efficiently delivers proteins into mouse and human T cells, as well as various tissues. Moreover, it enters the brain tissue and resident cells through blood vessels by penetrating the tightly organized blood–brain barrier. The dNP2-conjugated cytoplasmic domain of cytotoxic T-lymphocyte antigen 4 (dNP2-ctCTLA-4) negatively regulates activated T cells and shows inhibitory effects on experimental autoimmune encephalomyelitis in both preventive and therapeutic mouse models, resulting in the reduction of demyelination and CNS-infiltrating T helper 1 and T helper 17 cells. Thus, this study demonstrates that dNP2 is a blood–brain barrier-permeable peptide and dNP2-ctCTLA-4 could be an effective agent for treating CNS inflammatory diseases such as MS.

来源: Nature Communications 浏览次数:0

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