TY - JOUR
T1 - Glycosphingolipids - Sweets for botulinum neurotoxin
AU - Yowler, Brian C.
AU - Schengrund, Cara Lynne
N1 - Funding Information:
This work was supported in part by award number DAMD17-02-1-0676 from the US Army Medical Research and Materiel Command.
PY - 2004
Y1 - 2004
N2 - A number of viruses, bacteria, and bacterial toxins can only act on cells that express the appropriate glycosphingolipids (GSLs) on the outer surface of their plasma membranes. An example of this dependency is provided by botulinum neurotoxin (BoNT) which is synthesized by Clostridium botulinum and inhibits neurotransmission at the neuromuscular junction by catalyzing hydrolysis of a SNARE protein, thereby inducing a flaccid paralysis. Haemagglutinin components of progenitor forms of BoNT mediate its adherence to glycosphingolipids (GSLs) on intestinal epithelial cells while the cellular activity of most isolated serotypes requires the presence of certain gangliosides, especially those of the Gg1b family. This review discusses available information about the identity and the roles of GSLs in the activity of BoNT. Observations that serotypes A-F of BoNT require gangliosides for optimum activity (serotype G apparently does not), permits the hypothesis that it should be possible to develop an antagonist of this interaction thereby inhibiting/reducing its effect.
AB - A number of viruses, bacteria, and bacterial toxins can only act on cells that express the appropriate glycosphingolipids (GSLs) on the outer surface of their plasma membranes. An example of this dependency is provided by botulinum neurotoxin (BoNT) which is synthesized by Clostridium botulinum and inhibits neurotransmission at the neuromuscular junction by catalyzing hydrolysis of a SNARE protein, thereby inducing a flaccid paralysis. Haemagglutinin components of progenitor forms of BoNT mediate its adherence to glycosphingolipids (GSLs) on intestinal epithelial cells while the cellular activity of most isolated serotypes requires the presence of certain gangliosides, especially those of the Gg1b family. This review discusses available information about the identity and the roles of GSLs in the activity of BoNT. Observations that serotypes A-F of BoNT require gangliosides for optimum activity (serotype G apparently does not), permits the hypothesis that it should be possible to develop an antagonist of this interaction thereby inhibiting/reducing its effect.
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U2 - 10.1023/B:GLYC.0000046271.64647.fd
DO - 10.1023/B:GLYC.0000046271.64647.fd
M3 - Review article
C2 - 15514477
AN - SCOPUS:7244248860
SN - 0282-0080
VL - 21
SP - 287
EP - 293
JO - Glycoconjugate Journal
JF - Glycoconjugate Journal
IS - 6
ER -