Mechanisms of Action of Clostridial Neurotoxins on Dissociated Mouse Spinal Cord Neurons in Cell Culture
Final rept. 1 Jan 86-31 Dec 89
MARYLAND UNIV BALTIMORE
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Although the clostridial neurotoxin tetanus toxin is one of the most potent biological substances, little is known about its specific mechanisms of action. The toxin is a 150,000 mw. bacterial protein comprised of two chains, the amino acid structure has been elucidated Eisel et al., 1986. A binding subunit is located on the carboxyterminal of the 96,000 m.w. heavy chain. The papain produced fragment fragment C containing this binding subunit is not toxic, but binding is necessary for the toxin to gain access to the intracellular compartment where the toxin is active. In the intact animal tetanus toxin in the periphery binds to local and remote nerve terminals and then is transported retrograde to the spinal cord Price et al., 1975. Once in the motoneurons, the toxin then moves transsynaptically to the presynaptic terminals synapsing on the mononeurons Schawb et al., 1976, 1979. The clinical picture of tetanus is one of disinhibition. It has been speculated for some time that tetanus toxin might preferentially affect inhibitory neurons, with perhaps a specificity for glycinergic synapses.
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