- Letter to the Editor
- Open Access
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
- Botulinum Toxin
- Cluster Headache
- Cholera Toxin
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].
- Sostak P, Krause P, Forderreuther S et al (2007) Botulinum toxin type-A therapy in cluster headache: an open study. J Headache Pain 8(4):236–241. doi:10.1007/s10194-007-0400-0PubMed CentralView ArticlePubMedGoogle Scholar
- Martelletti P, Granata M, Giacovazzo M (1993) Serum interleukin-1 beta is increased in cluster headache. Cephalalgia 13(5):343–345View ArticlePubMedGoogle Scholar
- Martelletti P (2000) Proinflammatory pathways in cervicogenic headache. Clin Exp Rheumatol 18(2 Suppl 19):S33–38PubMedGoogle Scholar
- Holbourn KP, Sutton JM, Shore C et al (2005) Molecular recognition of an ADP-ribosy1 transferase; clostridium C3 exoenzyme. Proc Natl Acad Sci 102(15):5357–5362PubMed CentralView ArticlePubMedGoogle Scholar
- Harmey D, Stenbeck G, Nobes CD et al (2004) Regulation of osteoblast differentiation by pasteurella multocida toxin (PMT): a role for Rho GTPase in bone formation. J Bone Miner Res 19(4):661–667View ArticlePubMedGoogle Scholar
- Singh R, Wang B, Shirraikar A, et al (1999) The IL-1 receptor and Rho directly associate to drive cell activation inflammation. J Clin Invest 103(11):1561–1570PubMed CentralView ArticlePubMedGoogle Scholar