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

Download

index.pdf

Date

2014-03-01

Author

Kiriş, Erkan
Burnett, JC
Soloveva, V
Kane, CD
Bavari, S

Metadata

Show full item record

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Item Usage Stats

219
views

127
downloads

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.

Subject Keywords

Botulinum neurotoxin, Cell-based assays, Embryonic stem cells, Motor neurons, Drug discovery, High-throughput screening, High-content imaging, ELISA, MSD, Phenotypic screening

URI

https://hdl.handle.net/11511/38223

Journal

Expert review of molecular diagnostics

DOI

https://doi.org/10.1586/14737159.2014.867808

Collections

Department of Biology, Article

Suggestions

OpenMETU
Core

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...
Evaluation of methylation profiles of an epidermal growth factor receptor gene in a head and neck squamous cell carcinoma patient group Mutlu, M.; Mutlu, Pelin; Azarkan, S.; Baylr, Ö.; Öcal, B.; Saylam, G.; KORKMAZ, MEHMET HAKAN (2021-03-23) Upregulation of the epidermal growth factor receptor (EGFR) gene has shown an important impact on the development of head and neck cancers due to its important regulation role on multiple cell signaling pathways. The aim of this study was to investigate the methylation pattern of the promoter region of the EGFR gene between head and neck squamous cell carcinoma (HNSCC) patients and a control group. Forty-seven unrelated HNSCC patients, clinically diagnosed at the Department of Otorhinolaryngology, Dlşkapl Y...
Expanding the Clinical and Immunological Phenotypes and Natural History of MALT1 Deficiency Sefer, Asena Pinar; et. al. (2022-01-01) Purpose MALT1 deficiency is a combined immune deficiency characterized by recurrent infections, eczema, chronic diarrhea, and failure to thrive. Clinical and immunological characterizations of the disease have not been previously reported in large cohorts. We sought to determine the clinical, immunological, genetic features, and the natural history of MALT-1 deficiency. Methods The clinical findings and treatment outcomes were evaluated in nine new MALT1-deficient patients. Peripheral lymphocyte subset anal...
Antioxidant capacities and bioactive compounds of novel thermo-tolerant green microalgae Bulut, Onur; Öktem, Hüseyin Avni; Department of Biotechnology (2018) Accumulation of reactive oxygen species (ROS) at high levels in cells as a result of normal cellular activities as well as exposure to oxidative stress is attributed to many chronic degenerative diseases and conditions in humans including cardiovascular diseases, cancer and aging-related conditions such as Alzheimer's disease. Although living organisms are equipped with enzymatic and non-enzymatic antioxidant defense systems to counteract the adverse effects of oxidative stress, yet they rely on exogenous s...
Investigation of docetaxel and doxorubicin resistance in mcf-7 breast carcinoma cell line Darcansoy İşeri, Özlem; Gündüz, Ufuk; Department of Biotechnology (2009) 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...

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: https://hdl.handle.net/11511/38223.