Botulinum toxin type-A therapy in cluster headache: a novel molecular mechanism
© Springer-Verlag 2008
Received: 25 January 2008
Accepted: 4 February 2008
Published: 26 February 2008
I read with great interest the article by Sostak et al. .
This work shows that botulinum toxin markedly suppresses cluster headache. I would like to complete the discussion of Sostak et al.  by introducing a major route through which botulinum toxin could suppress cluster headache.
Interleukin-1 is a potent prototypical pro-inflammatory cytokine implicated in the pathogenesis of cluster headache [2, 3]. Therefore, as described below, the botulinum toxin minimizes headache by inactivating interleukin-1.
Bacteria produce many enzymes that show extraordinary specificity for mammalian intracellular proteins. The specificity of these bacterial enzymes has not only made them a valuable tool for elucidating the cellular functions of their targets but has also increased our understanding of protein interactions .Clostridium botulinum is no exception, producing two classes of enzymes that have very specific protein targets, neurotoxin A–G and the ADP-ribosyltransferases C2, C3 bot 1 and C3 bot 2 . C2 and C3 bot are a part of a larger family of ADP-ribosylating toxins, including diphtheria toxin and cholera toxin, which cleave NAD and transfer ADP-ribose to target proteins. Although the members of this family have homologous enzymatic domains and similar active sites, these toxins ribosylate ADP and therefore, disable a range of cellular targets . Rho family GTPases control the assembly of both cell–matrix and cell–cell adhesion complexes. IL-1 receptor signaling complex contains these G proteins, and Rho GTPase is an essential unit for the activation of IL-1 inflammatory pathway. C3 transferase exonzyme specifically inhibits Rho GTPase by ADP-ribosylation of amino acid asparagine-41 [5, 6].
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