Tetanus toxin 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 by using dyneins.
Tetanus toxin is an extremely potent neurotoxin produced by the vegetative cell 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 also called spasmogenic toxin, or TeNT. The LD50 of this toxin has been measured to be approximately 1 ng/kg, making it second only to Botulinum toxin as the deadliest toxin in the world. However, these tests are conducted solely on mice which may react to the toxin differently from humans and other animals.
C. Tetani also produces the exotoxin tetanolysin, a hemolysin, that causes destruction of tissues.
The mechanism of TeNT action can be broken down and discussed in 6 different steps.
- Transport
- Specific binding in the periphery neurons
- Retrograde axonal transport to the central nervous system (CNS) inhibitory interneurons
- Transcytosis from the axon into the inhibitory interneurons
- Action
- Temperature and pH mediated translocation of the light chain into the cytosol
- Reduction of the disulphide bond between the light and heavy chain
- Cleavage of synaptobrevin
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