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Updated: May 2, 2026
A High-throughput-compatible FRET-based Platform for Identification and Characterization of Botulinum Neurotoxin Light Chain Modulators
Published on: December 27, 2013
Persistence of botulinum neurotoxin a subtypes 1-5 in primary rat spinal cord cells
Regina Clare Meyer Whitemarsh1, William Howard Tepp1, Eric Arthur Johnson1
1Department of Bacteriology, University of Wisconsin - Madison, Madison, Wisconsin, United States of America.
Abstract:
Botulinum neurotoxins (BoNTs) are the most poisonous substances known and cause the severe disease botulism. BoNTs have also been remarkably effective as therapeutics in treating many neuronal and neuromuscular disorders. One of the hallmarks of BoNTs, particularly serotype A, is its long persistence of 2-6 months in patients at concentrations as low as fM or pM. The mechanisms for this persistence are currently unclear. In this study we determined the persistence of the BoNT/A subtypes 1 through 5 in primary rat spinal neurons. Remarkably, the duration of intracellular enzymatic activity of BoNT/A1, /A2, /A4 and /A5 was shown to be at least 10 months. Conversely, the effects of BoNT/A3 were observed for up to ∼5 months. An intermittent dosing with BoNT/E showed intracellular activity of the shorter acting BoNT/E for 2-3 weeks, followed by reoccurrence and persistence of BoNT/A-induced SNAP-25 cleavage products.
