Mechanism of Action of the Presynaptic Neurotoxin Tetanus Toxin
Final rept. 1 Jul 1990-31 Dec 1993
MARYLAND UNIV BALTIMORE SCHOOL OF MEDICINE
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The goal of this project was to identify molecular mechanisms of action of Clostridial neurotoxins so that effective therapeutic agents could be developed. In several experimental series effects of Clostridial neurotoxins on protein kinase C and cGMP phosphodiesterase activities was examined in cultured neural cells, the PCl 2 cell line. In precise experiments it was shown that these enzyme systems are not targets for the toxins. Further studies showed that these cells expressed different modes or pathways of neurosecretion of neurotransmitter. Importantly, series of focused experiments revealed that only one mode was inhibited by Clostridial neurotoxins. In most recent studies, antibodies against different botulinum neurotoxin serotypes were used to identify homologues of botulinum toxins in neural cells. Several specific proteins have indeed been identified in PCl 2 cells. These results have significance with respect to the development of effective drugs that will specifically block the action of exogenous toxin, while sparing the activities of endogenous homologues. Botulinum toxin, Clostridial neurotoxins, Synaptic transmission, Botulinum toxin antibodies, Phosphodiesterase, RA 4.
- Medicine and Medical Research