Skip NavigationSkip to Content
Return Return to Search Results

Embryonic stem cell-derived motoneurons provide a highly sensitive cell culture model for botulinum neurotoxin studies, with implications for high-throughput drug discovery

  1. Author:
    Kiris, E.
    Nuss, J. E.
    Burnett, J. C.
    Kota, K. P.
    Koh, D. C.
    Wanner, L. M.
    Torres-Melendez, E.
    Gussio, R.
    Tessarollo, L.
    Bavari, S.

  2. Author Address

    [Kiris, E; Nuss, JE; Kota, KP; Wanner, LM; Torres-Melendez, E; Bavari, S] USA, Med Res Inst Infect Dis, Dept Target Discovery & Expt Microbiol, Frederick, MD 21702 USA [Kiris, E; Koh, DC; Tessarollo, L] NCI, Neural Dev Grp, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA [Burnett, JC] NCI, SAIC Frederick Inc, TSBDDG, Frederick, MD 21702 USA [Burnett, JC; Gussio, R] NCI, TSBDDG, Informat Technol Branch, Dev Therapeut Program, Frederick, MD USA;Bavari, S (reprint author), USA, Med Res Inst Infect Dis, Dept Target Discovery & Expt Microbiol, 1425 Porter St, Frederick, MD 21702 USA;sina.bavari@amedd.army.mil
    1. Year: 2011
    2. Date: May
  2. Journal: Stem Cell Research
    1. 6
    2. 3
    3. Pages: 195-205
  4. Type of Article: Article
  5. ISSN: 1873-5061
  1. Abstract:

    Botulinum neurotoxins (BoNTs) inhibit cholinergic synaptic transmission by specifically cleaving proteins that are crucial for neurotransmitter exocytosis. Due to the lethality of these toxins, there are elevated concerns regarding their possible use as bioterrorism agents. Moreover, their widespread use for cosmetic purposes, and as medical treatments, has increased the potential risk of accidental overdosing and environmental exposure. Hence, there is an urgent need to develop novel modalities to counter BoNT intoxication. Mammalian motoneurons are the main target of BoNTs; however, due to the difficulty and poor efficiency of the procedures required to isolate the cells, they are not suitable for high-throughput drug screening assays. Here, we explored the suitability of embryonic stem (ES) cell-derived motoneurons as a renewable, reproducible, and physiologically relevant system for BoNT studies. We found that the sensitivity of ES-derived motoneurons to BoNT/A intoxication is comparable to that of primary mouse spinal motoneurons. Additionally, we demonstrated that several BoNT/A inhibitors protected SNAP-25, the BoNT/A substrate, in the ES-derived motoneuron system. Furthermore, this system is compatible with immunofluorescence-based high-throughput studies. These data suggest that ES-derived motoneurons provide a highly sensitive system that is amenable to large-scale screenings to rapidly identify and evaluate the biological efficacies of novel therapeutics. Published by Elsevier B.V.

    See More

  1. Keywords:

External Sources

  1. View Full Text
  2. DOI: 10.1016/j.scr.2011.01.002
  3. View record in Web of Science®
  4. WOS: 000291295800001

Library Notes

  1. Fiscal Year: FY2010-2011
NCI at Frederick

You are leaving a government website.

This external link provides additional information that is consistent with the intended purpose of this site. The government cannot attest to the accuracy of a non-federal site.

Linking to a non-federal site does not constitute an endorsement by this institution or any of its employees of the sponsors or the information and products presented on the site. You will be subject to the destination site's privacy policy when you follow the link.

ContinueCancel