Exploration of endogenous substrate cleavage by various forms of botulinum neurotoxins

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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Author(s)

  • Jiubiao Guo
  • Jinglin Wang
  • Edward Waichi Chan
  • Sheng Chen

Detail(s)

Original languageEnglish
Article number5062
Pages (from-to)42-45
Journal / PublicationToxicon
Volume100
Online published22 Apr 2015
Publication statusPublished - 15 Jun 2015
Externally publishedYes

Abstract

Abstract Botulinum neurotoxins are the most potent protein neurotoxin known to human. The dual roles of BoNTs as both the causative agent of human botulism and a widely used protein-based therapeutic agent for treatment of numerous neuromuscular disorders/cosmetic uses make it an extremely hot topic of research. Biochemical characterization of these toxins was mainly confined to the recombinant light chains and substrate and little is known about their efficiency on the cleavage of endogenous substrates. In the present study, we showed that BoNTs exhibited variable activities on their endogenous substrates and that their efficiency to cleave recombinant and endogenous substrate was not consistent, presumably due to the differential recognition of their respective substrates in the natural SNARE complex format. Through testing the combinatorial effects of different BoNTs on cleavage of endogenous substrates, we showed that the combinations of LC/A and LC/B, as well as LC/A and LC/F, could enhance the activity of each individual BoNT. This finding may shed light on the future development of new BoNT serotypes for clinical application, and formulation of combinatorial uses of different BoNTs to minimize the development of immuno-resistance by using a lower amount of individual type.

Research Area(s)

  • Botulinum neurotoxins, Combinational uses, Endogenous substrate cleavage, Therapeutic application

Citation Format(s)

Exploration of endogenous substrate cleavage by various forms of botulinum neurotoxins. / Guo, Jiubiao; Wang, Jinglin; Chan, Edward Waichi; Chen, Sheng.

In: Toxicon, Vol. 100, 5062, 15.06.2015, p. 42-45.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review