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取得进展:针对肉毒神经毒素的治疗方法的检测。

Gaining ground: assays for therapeutics against botulinum neurotoxin.

机构信息

Faculty Research Participation Program, Oak Ridge Associated Universities, Belcamp, MD, USA.

出版信息

Trends Microbiol. 2010 Apr;18(4):164-72. doi: 10.1016/j.tim.2010.02.001. Epub 2010 Mar 4.

DOI:10.1016/j.tim.2010.02.001
PMID:20202845
Abstract

Owing in part to recently heightened concern over bioterrorism, interest in the mechanism of action of botulinum neurotoxin (BoNT) and development of effective therapeutic strategies has dramatically increased. The emergence of BoNT as an effective treatment for a variety of neurological disorders and its growing use in the cosmetic industry have also increased interest in developing effective countermeasures. Although recent attempts to create effective vaccines appear promising, the multitude of clinical and cosmetic uses of BoNT make mass vaccination against the toxin undesirable and impractical, leading to intensified efforts to develop effective therapeutics to combat large-scale intoxications. In this review, we examine the relevant and available in vitro cell-based assays and in vivo assays for drug discovery and development, especially with regard to the potential for medium- to high-throughput automation and its use in identifying physiologically relevant inhibitors.

摘要

部分由于最近对生物恐怖主义的关注度提高,人们对肉毒杆菌神经毒素 (BoNT) 的作用机制和有效治疗策略的开发产生了浓厚的兴趣。BoNT 作为治疗各种神经疾病的有效药物的出现,以及其在化妆品行业的日益广泛应用,也增加了人们开发有效对策的兴趣。尽管最近开发有效疫苗的尝试似乎很有希望,但 BoNT 的多种临床和美容用途使得针对该毒素进行大规模疫苗接种变得不可取和不切实际,这导致人们加紧努力开发有效的治疗方法来对抗大规模中毒。在这篇综述中,我们检查了用于药物发现和开发的相关体外基于细胞的测定法和体内测定法,特别是在中等至高通量自动化的潜力及其在识别生理相关抑制剂方面的应用。

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引用本文的文献

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PLoS One. 2015 Jun 10;10(6):e0129264. doi: 10.1371/journal.pone.0129264. eCollection 2015.
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SRC family kinase inhibitors antagonize the toxicity of multiple serotypes of botulinum neurotoxin in human embryonic stem cell-derived motor neurons.
Src家族激酶抑制剂可拮抗多种血清型肉毒杆菌神经毒素对人胚胎干细胞衍生运动神经元的毒性作用。
Neurotox Res. 2015 May;27(4):384-98. doi: 10.1007/s12640-015-9526-z. Epub 2015 Mar 18.
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A high content imaging assay for identification of Botulinum neurotoxin inhibitors.一种用于鉴定肉毒杆菌神经毒素抑制剂的高内涵成像分析方法。
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