Promising new approaches for treatment of botulinum intoxication

The botulinum neurotoxins (BoNTs) comprise a family of seven immunologically distinct proteins (A–G) produced by discrete strains of the anaerobic bacterium Clostridium botulinum. 1,2 These toxins act on peripheral cholinergic synapses of the neuromuscular junction and autonomic ganglia to inhibit spontaneous and impulsedependent release of acetylcholine. 1–3 Intoxication by BoNT results in muscle weakness, which can be fatal when the diaphragm and intercostal muscles become sufficiently compromised to impair ventilation. The clostridial neurotoxins are synthesized as ca. 150-kDa single-chain protoxins. They are activated to form dichain proteins consisting of a ca. 50-kDa light chain and a ca. 100-kDa heavy chain. 4

[1]  P. Jahrling,et al.  Clinical recognition and management of patients exposed to biological warfare agents. , 2001, Clinics in laboratory medicine.

[2]  R. Stevens,et al.  Crystal structure of botulinum neurotoxin type A and implications for toxicity , 1998, Nature Structural Biology.

[3]  R. Stafford,et al.  Type A botulinum neurotoxin proteolytic activity: development of competitive inhibitors and implications for substrate specificity at the S1′ binding subsite , 1998, FEBS letters.

[4]  M. Adler,et al.  Efficacy of a novel metalloprotease inhibitor on botulinum neurotoxin B activity , 1998, FEBS letters.

[5]  W. Tepp,et al.  Status of Cys Residues in the Covalent Structure of Botulinum Neurotoxin Types A, B, and E , 1998, Journal of protein chemistry.

[6]  M. Adler,et al.  Structural features of aminoquinolines necessary for antagonist activity against botulinum neurotoxin. , 1997, Toxicon : official journal of the International Society on Toxinology.

[7]  M. Adler,et al.  Efficacy of certain quinolines as pharmacological antagonists in botulinum neurotoxin poisoning. , 1997, Toxicon : official journal of the International Society on Toxinology.

[8]  J. Dolly,et al.  Botulinum neurotoxin C1 cleaves both syntaxin and SNAP-25 in intact and permeabilized chromaffin cells: correlation with its blockade of catecholamine release. , 1996, Biochemistry.

[9]  G. Schiavo,et al.  The mechanism of action of tetanus and botulinum neurotoxins. , 1995, Archives of toxicology. Supplement. = Archiv fur Toxikologie. Supplement.

[10]  R. Jahn,et al.  Inhibition of neurotransmitter release by clostridial neurotoxins correlates with specific proteolysis of synaptosomal proteins , 1994, Journal of Physiology-Paris.

[11]  T. Südhof,et al.  Synaptic vesicle membrane fusion complex: action of clostridial neurotoxins on assembly. , 1994, The EMBO journal.

[12]  G. Schiavo,et al.  Botulinum G neurotoxin cleaves VAMP/synaptobrevin at a single Ala-Ala peptide bond. , 1994, The Journal of biological chemistry.

[13]  C. Montecucco,et al.  Mechanism of action of tetanus and botulinum neurotoxins , 1994, Molecular microbiology.

[14]  R. Jahn,et al.  Clostridial neurotoxins: new tools for dissecting exocytosis. , 1994, Trends in cell biology.

[15]  T. Südhof,et al.  Proteolysis of SNAP-25 by types E and A botulinal neurotoxins. , 1994, The Journal of biological chemistry.

[16]  Thomas C. Südhof,et al.  Botulinum neurotoxin A selectively cleaves the synaptic protein SNAP-25 , 1993, Nature.

[17]  G. Schiavo,et al.  Tetanus and botulism neurotoxins: a new group of zinc proteases. , 1993, Trends in biochemical sciences.

[18]  C. Schengrund,et al.  Adherence of botulinum and tetanus neurotoxins to synaptosomal proteins , 1992, Brain Research Bulletin.

[19]  L. Tauc,et al.  Minimal essential domains specifying toxicity of the light chains of tetanus toxin and botulinum neurotoxin type A. , 1992, The Journal of biological chemistry.

[20]  Y. Kamata,et al.  Lectins from Triticum vulgaris and Limax flavus are universal antagonists of botulinum neurotoxin and tetanus toxin. , 1991, The Journal of pharmacology and experimental therapeutics.

[21]  B. Ehrlich,et al.  Channels formed by botulinum, tetanus, and diphtheria toxins in planar lipid bilayers: relevance to translocation of proteins across membranes. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[22]  P. Hanson,et al.  Membrane fusion: SNAREs line up in new environment , 1998, Nature.

[23]  L. Simpson.  CHAPTER 7 – Peripheral Actions of the Botulinum Toxins , 1989 .

[24]  E. Habermann,et al.  Clostridial neurotoxins: handling and action at the cellular and molecular level. , 1986, Current topics in microbiology and immunology.