The use of small molecules to investigate molecular mechanisms and therapeutic targets for treatment of botulinum neurotoxin A intoxication.
Botulinum neurotoxins (BoNTs) are agents responsible for botulism, a disease characterized by peripheral neuromuscular blockade and subsequent flaccid paralysis. The potent paralytic ability of these toxins has resulted in their use as a therapeutic; however, BoNTs are also classified by the Centers for Disease Control and Prevention as one of the six highest-risk threat agents of bioterrorism. Consequently, a thorough understanding of the molecular mechanism of BoNT toxicity is crucial before effective inhibitors and, ultimately, an approved drug can be developed. In this article, we systematically detail BoNT intoxication by examining each of the discrete steps in this process. Additionally, rationally designed strategies for combating the toxicity of the most potent BoNT serotype are evaluated.
Dickerson
Tobin J
TJ
Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, and Worm Institute for Research and Medicine (WIRM), The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA. tobin@scripps.edu
Janda
Kim D
KD
D000818:Animals; D023482:Bioterrorism / Q000517:prevention & control; D019274:Botulinum Toxins, Type A / Q000633:toxicity*; D001906:Botulism / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans
D019274:Botulinum Toxins, Type A