Retargeted Clostridial Neurotoxins as Novel Agents for Treating Chronic Diseases

被引:7
|
作者
Yeh, Felix L. [1 ]
Zhu, Yiming [2 ]
Tepp, William H. [3 ]
Johnson, Eric A. [3 ]
Bertics, Paul J. [2 ]
Chapman, Edwin R. [1 ]
机构
[1] Univ Wisconsin, Dept Neurosci, Howard Hughes Med Inst, Madison, WI 53706 USA
[2] Univ Wisconsin, Dept Biomol Chem, Madison, WI 53706 USA
[3] Univ Wisconsin, Dept Bacteriol, Madison, WI 53706 USA
关键词
TUMOR-NECROSIS-FACTOR; NEUROTRANSMITTER RELEASE; IN-VITRO; BOTULINUM; EXPRESSION; CYTOKINES; STRATEGY; PROTEIN; TARGET; TOXIN;
D O I
10.1021/bi201490t
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Botulinum neurotoxin (BoNT) A and B are used to treat neuropathic disorders; if retargeted, these agents could be used to treat medical conditions that involve secretion from nonneuronal cells. Here, we report novel strategies for successfully retargeting BoNTs, and also tetanus neurotoxin (TeNT), to primary human blood monocyte-derived macrophages where BoNT/B inhibited the release of tumor necrosis factor-alpha, a cytokine that plays a key role in inflammation. Furthermore, mice treated with retargeted BoNT/B exhibited a significant reduction in macrophage (M Phi) recruitment, indicating that these toxins can be used to treat chronic inflammation.
引用
收藏
页码:10419 / 10421
页数:3
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