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

Kiriş, Erkan
Burnett, JC
Soloveva, V
Kane, CD
Bavari, S
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 costefficient 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 cellbased assays and high-throughput screening approaches for the identification of both direct and indirect BoNT inhibitors.
Expert review of molecular diagnostics


SRC family kinase inhibitors antagonize the toxicity of multiple serotypes of botulinum neurotoxin in human embryonic stem cell-derived motor neurons.
Kiriş, Erkan; Nuss, JE; Wanner, LM; Peyser, BD; Du, HT; Gomba, GY; Kota, KP; Panchal, RG; Gussio, R; Kane, CD; Tessarollo, L; Bavari, S (2015-05-01)
Botulinum neurotoxins (BoNTs), the causative agents of botulism, are potent inhibitors of neurotransmitter release from motor neurons. There are currently no drugs to treat BoNT intoxication after the onset of the disease symptoms. In this study, we explored how modulation of key host pathways affects the process of BoNT intoxication in human motor neurons, focusing on Src family kinase (SFK) signaling. Motor neurons derived from human embryonic stem (hES) cells were treated with a panel of SFK inhibitors a...
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Multidrug resistance phenotype of tumor cells describes resistance to wide range of structurally unrelated anticancer agents and is a serious limitation to effective chemotherapy. It is a multifactor yet not fully elucidated phenomenon by the involvement of diverse cellular pathways. Aim of this study was to investigate the resistance mechanisms developed against docetaxel and doxorubicin that are widely used in the treatment of breast cancer in model cell line MCF-7. Resistant sublines were developed by ap...
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One of the main problems of current cancer chemotherapy is the lack of selectivity of anti-cancer drugs to tumor cells which leads to systemic toxicity and adverse side effects. In order to overcome these limitations, researches on controlled drug delivery systems have gained much attention. Nanoscale based drug delivery systems provide tumor targeting. Among many types of nanocarriers, superparamagnetic nanoparticles with their biocompatible polymer coatings can be targeted to an intented site by an extern...
Citation Formats
E. Kiriş, J. Burnett, V. Soloveva, C. Kane, and S. Bavari, “Recent developments in cell-based assays and stem cell technologies for botulinum neurotoxin research and drug discovery.,” Expert review of molecular diagnostics, pp. 153–68, 2014, Accessed: 00, 2020. [Online]. Available: