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( Tetanospasmin)
Tetanospasmin is the neurotoxin produced by the vegetative spore of Clostridium tetani in anaerobic conditions, causing tetanus. It has no known function for clostridia in the soil environment where they are normally encountered. It is sometimes called spasmogenic toxin, tetanus toxin or abbreviated to TeTx or TeNT. Tetanospasmin spreads through tissue spaces into the lymphatic and vascular systems. It enters the nervous system at the neuromuscular junctions and migrates through nerve trunks and into the central nervous system (CNS) by retrograde axonal transport. The peptide tetanospasmin has a molecular weight of 150kDa. It is made up of two parts a 100kDa heavy or B-chain and a 50kDa light or A-chain. The chains are connected by a disulfide bond. The B-chain binds to disialogangliosides (GD2 and GD1b) on the neurone membrane. The A-chain, a zinc endopeptidase, attacks the vesicle-associated membrane protein (VAMP). This stops the affected neurons from releasing the inhibitory neurotransmitters GABA (gamma-aminobutyric acid) and glycine by degrading the protein synaptobrevin. The consequence of this is dangerous overactivity in the muscles from the smallest stimulus-- the failure of inhibition of motor reflexes by sensory stimulation. This causes generalized contractions of the agonist and antagonist musculature, termed a tetanic spasm. Tetanic spasms can occur in a distinctive form called opisthotonos and be sufficiently severe to fracture long bones. The shorter nerves are the first to be inhibited, which leads to the characteristic early symptoms in the face and jaw, risus sardonicus and lockjaw.
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