Home >> Future Microbiology, Volume 2, Number 6

Investigating novel therapeutic targets and molecular mechanisms to treat botulinum neurotoxin A intoxication

Authors: Eubanks, Lisa M; Dickerson, Tobin J

Source: Future Microbiology, Volume 2, Number 6, December 2007 , pp. 677-687(11)

Publisher: Future Medicine

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Abstract:

Botulinum neurotoxin (BoNT) has recently catapulted into the public consciousness in two seemingly disparate roles: potential use as a biological weapon and treatment of neuromuscular disorders. This bacterially produced protein is the most potent toxin known to humans, with a lethal dose estimated at approximately 1 ng/kg of body weight. BoNT intoxication occurs via a multistep process that includes recognition of peripheral neuronal cell membrane receptors, endocytosis and translocation of the light chain metalloprotease into the cytosol, and catalytic cleavage of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins critical for vesicle fusion and neurotransmitter release. Each of these distinct steps has been studied at the molecular level and is a valid target for the development of pharmacological interventions to prevent the considerable mortality associated with botulism. Alternatively, clinical uses of BoNT continue to expand at an ever-increasing rate; however, further optimization of BoNT therapy is critical to maximize efficacy.
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