Recent developments in cell-based assays and stem cell technologies for botulinum neurotoxin research and drug discovery.

Recent developments in cell-based assays and stem cell technologies for botulinum neurotoxin research and drug discovery.
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DOI:
10.1586/14737159.2014.867808
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发表时间:
2014-03
影响因子:
5.1
通讯作者:
Bavari S
Bavari S
中科院分区:
医学3区
文献类型:
--
作者:
Kiris E;Kota KP;Burnett JC;Soloveva V;Kane CD;Bavari S

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肉毒杆菌神经毒素(bont)是一种异常有效的神经传递抑制剂,可引起与肉毒杆菌中毒相关的肌肉麻痹和呼吸衰竭。目前,没有药物可用于对抗细胞内BoNT中毒。为了开发有效的医学治疗方法,基于细胞的测定提供了一个有价值的系统,以一种时间和成本效益的方式识别新的抑制剂。因此,包括永生化细胞、原代神经元和干细胞衍生神经元在内的细胞系统已经建立起来。干细胞来源的神经元对BoNT中毒高度敏感,是研究BoNT生物学效应的理想模型。稳健的免疫测定用于量化BoNT活性,并在抑制剂筛选过程中发挥核心作用。在这篇综述中,我们研究了生理学相关的基于细胞的检测和高通量筛选方法的最新进展,以识别直接和间接的BoNT抑制剂。
Botulinum neurotoxins (BoNTs) are exceptionally potent inhibitors of neurotransmission, causing muscle paralysis and respiratory failure associated with the disease botulism. Currently, no drugs are available to counter intracellular BoNT poisoning. To develop effective medical treatments, cell-based assays provide a valuable system to identify novel inhibitors in a time- and cost-efficient manner. Consequently, cell-based systems including immortalized cells, primary neurons, and stem-cell derived neurons have been established. Stem cell-derived neurons are highly sensitive to BoNT intoxication and represent an ideal model to study the biological effects of BoNTs. Robust immunoassays are used to quantify BoNT activity and play a central role during inhibitor screening. In this review, we examine recent progress in physiologically relevant cell-based assays and high-throughput screening approaches for the identification of both direct and indirect BoNT inhibitors.
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