Faculty Research Participation Program, Oak Ridge Associated Universities, Belcamp, MD, USA.
Trends Microbiol. 2010 Apr;18(4):164-72. doi: 10.1016/j.tim.2010.02.001. Epub 2010 Mar 4.
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.
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。