Investigation of 'CRATKML' derived peptides as antidotes for the in vivo and in vitro paralytic effect of botulinum neurotoxin A. (18th March 2011)

• Record Type: Journal Article
• Authors: Potian, Joseph G.; Thyagarajan, Baskaran; Hognason, Kormakur; Lebeda, Frank J.; Schmidt, James; Adler, Michael; McArdle, Joseph
• Is Part Of: Botulinum journal. Volume 1:Number 4(2010)
• Page Start: 407
• Page End: 417
• Publication Date: 2011-03-18
• Subjects: SNAP25 -- MEI -- metalloendoprotease inhibitors -- neurotransmitter release -- botulinum neurotoxin -- BoNT&amp -- #47 -- A -- BoNT -- botulism -- mouse -- diaphragm -- EDL -- extensor digitorum longus -- twitch tension -- secretory vesicles -- neuromuscular transmission -- motor nerve endings -- CRATKML-derived peptides; Botulinum toxin -- Periodicals; Clostridium botulinum -- Periodicals; Drug development -- Periodicals; 615.9529364
• Languages: English
• ISSNs: 1754-7318

Abstract

CRATKML-derived peptides (Cp) prevent Botulinum neurotoxin A (BoNT/A) cleavage of purified SNAP25. We tested the effects of four cell membrane permeable Cp analogs on BoNT/A poisoned neuromuscular junctions. In vitro pretreatment with these Cps did not prevent BoNT/A inhibition of neuromuscular transmission (NMT). In vivo pretreatment with these Cps did not protect NMT against BoNT/A. The lack of prophylactic effect paralleled a lack of therapeutic effect on BoNT/A intoxicated mice. These data demonstrate that although Cps are effective BoNT/A antagonists in cell free systems, they are not effective against in vitro or in vivo BoNT/A actions of motor nerve endings.