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Botulinum neurotoxin subtype A2 enters neuronal cells faster than subtype A1
Author(s) -
Pier Christina L.,
Chen Chen,
Tepp William H.,
Lin Guangyun,
Janda Kim D.,
Barbieri Joseph T.,
Pellett Sabine,
Johnson Eric A.
Publication year - 2011
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2010.11.045
Subject(s) - botulism , botulinum neurotoxin , neurotoxin , toxicity , clostridium botulinum , chemistry , toxin , cell , ganglioside , pharmacology , biology , biochemistry , microbiology and biotechnology , organic chemistry
Botulinum neurotoxins (BoNTs), the causative agent of human botulism, are the most potent naturally occurring toxins known. BoNT/A1, the most studied BoNT, is also used as an important biopharmaceutical. In this study, the biological activity of BoNT/A1 is compared to that of BoNT/A2 using neuronal cell models. The data obtained indicate faster and increased intoxication of neuronal cells by BoNT/A2 than BoNT/A1, and that the mechanism underlying this increased toxicity is faster and more efficient cell entry that is independent of ganglioside binding. These results have important implications for the development of new BoNT based therapeutics and BoNT countermeasures.