Botulinum neurotoxin subtype A2 enters neuronal cells faster than subtype A1

• Published in: FEBS letters Vol. 585; no. 1; pp. 199 - 206
• Main Authors: Pier, Christina L., Chen, Chen, Tepp, William H., Lin, Guangyun, Janda, Kim D., Barbieri, Joseph T., Pellett, Sabine, Johnson, Eric A.
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 03.01.2011
• Subjects: Animals; biopharmaceuticals; Blotting, Western; BoNT/A1; BoNT/A2; Botulinum neurotoxin; botulinum toxin; Botulinum Toxins, Type A - metabolism; Botulinum Toxins, Type A - pharmacokinetics; Botulinum Toxins, Type A - pharmacology; botulism; Cell based assay; Cell entry; Cell Line, Tumor; Cell Survival - drug effects; Cells, Cultured; Clostridium botulinum; Dose-Response Relationship, Drug; gangliosides; Gangliosides - metabolism; humans; Hydrolysis - drug effects; Microscopy, Fluorescence; natural toxicants; Neuron; neurons; Neurons - drug effects; Neurons - metabolism; poisoning; Protein Binding; rab5 GTP-Binding Proteins - metabolism; Rats; Spinal Cord - cytology; Synaptophysin - metabolism; Synaptosomal-Associated Protein 25 - metabolism; therapeutics; Time Factors; toxicity; Cell based assay; Cell entry; Botulinum neurotoxin; BoNT/A2; Neuron; BoNT/A1
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2010.11.045

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.