Small molecule inhibitors as countermeasures for botulinum neurotoxin intoxication.

Small molecule inhibitors as countermeasures for botulinum neurotoxin intoxication.
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DOI:
10.3390/molecules16010202
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发表时间:
2010-12-30
期刊:
Molecules (Basel, Switzerland)
影响因子:
--
通讯作者:
Bowlin TL
Bowlin TL
中科院分区:
其他
文献类型:
--
作者:
Li B;Peet NP;Butler MM;Burnett JC;Moir DT;Bowlin TL

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肉毒神经毒素(BoNT)是已知毒素中最有效的,被美国CDC列为A类生物威胁剂。SNARE蛋白的BoNT介导的蛋白水解抑制乙酰胆碱胞吐进入神经肌肉接头,导致危及生命的弛缓性麻痹。目前,BoNT中毒(导致疾病状态肉毒杆菌中毒)的唯一疗法包括实验性预防性抗体和长期支持性护理。因此,迫切需要鉴定和开发将用作预防剂和暴露后“拯救”治疗剂的抑制剂。本文综述了近年来发现和开发小分子抑制剂作为BoNT中毒的治疗对策的进展。
Botulinum neurotoxins (BoNTs) are the most potent of known toxins and are listed as category A biothreat agents by the U.S. CDC. The BoNT-mediated proteolysis of SNARE proteins inhibits the exocytosis of acetylcholine into neuromuscular junctions, leading to life-threatening flaccid paralysis. Currently, the only therapy for BoNT intoxication (which results in the disease state botulism) includes experimental preventative antibodies and long-term supportive care. Therefore, there is an urgent need to identify and develop inhibitors that will serve as both prophylactic agents and post-exposure ‘rescue’ therapeutics. This review focuses on recent progress to discover and develop small molecule inhibitors as therapeutic countermeasures for BoNT intoxication.
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