2. Outline  History  Uses  Toxin and Toxic Effects  Mechanisms of Action  Summary  Conclusion  References

3. Botulinum Toxin  We chose Botulinum toxin because it is considered the most powerful neurotoxin known to man.  Botulism, or Botulinum intoxication can cause serious effects such as paralysis and respiratory failure.  It is commonly used for a large assortment of cosmetic and medical ailments.

4. Where Does it Come From?  Botulinum toxin is a protein produced by the anaerobic, spore-forming bacterium Clostridium botulinum

5. What is Botulinum Toxin?  The active molecule consists of: Heavy Chain Polypeptide Light Chain Polypeptide - These Chains are connected via disulfide bond

6. History discovery  Botulinum was first described in the 18 th century, when people were getting food poisoning from eating improperly stored meat and blood sausage resulting in death.  The association between the food poisoning deaths and botulism was first made by Justinus Kerner.  It was later discovered that Botulinum caused paralysis, and the link was soon made that it might be possible to reduce over active muscles with the toxin.

7. History original uses  After the discovery that Botulinum may decrease over-active muscles, testing began by injecting into ocular muscles of monkeys and into the legs of chickens. The results appeared to conclude that injections into the muscular area resulted in decreased muscles spasms or dystonia, with limited toxic effects.

8. Uses current medicinal uses  Initial treatments of Botulinum were used to cure strabismus, or cross eyes  Also used to stop uncontrollable blinking, or blepharospasm  Later discoveries include uses for cerebral palsy, overactive sweating, muscle spasms and chronic migraines

9. Cosmetic uses  Botulinum Toxin is most currently known to the world as Botox. Its used cosmetically for a temporary decrease in brow lines and frown lines. Botox is injected under the skin in particular areas to remove wrinkles.  Minimal side effects of the injections currently appear to be a decrease in facial or emotional expression.

10. Exposure Pathway  Botulinum toxin is usually ingested by eating contaminated food.  Once in the stomach, it crosses membrane barriers to enter circulation  In circulation it moves into extracellular space to reach it’s target, neurons.

11. Mechanism of Action  Botulinum toxin utilizes an AB mechanism.  There is a Heavy Chain and a Light Chain.  The Heavy Chain binds to proteins on the surface of axon terminals.  The toxin is then Endocytosed  Heavy Chain forms channel in endosome which the light chain moves through into the cytoplasm  Light Chain has proteolytic activity, and degrades integral proteins of SNARE complex  SNARE complex is required for the binding of neuro-secretory vesicles to the nerve synapse plasma membrane.  With no binding of neuro-secretory vesicles to plasma membrane, Acetocholine is unable to be released into neuromuscular junction  RESULT: PARALYSIS

12. Botulinum Toxin  The non-covalent complex is then connected to auxiliary proteins described as hemaggluttinins and nonhemaggluttinins. These proteins help the complex retain PH resistance allowing it to maintain function in the gut.

13. Symptoms  Muscle weakness in the facial region, including the inability to blink, swallow, chew or talk.  Blurred Vision  Muscle weakness in body.  Constipation  Difficulty breathing leading to respiratory failure.

14. Toxic variability  The Botulinum toxin is one the deadliest toxins known, and effects are seen in small doses  90 nanograms of the toxin could be lethal enough to kill a 200lb man  Botulinum consists of seven different serotypes  Serotype A has the lengthiest duration of action and appears to be considered the most toxic form

15. Prevention of Botulism  Preserving Foods using heat, pressure and low pH Spores can be inactivated at 120 Celsius High pressure kills spores High pH favors spore germination The toxin can be inactivated be heating at temperatures greater than 85 degrees C for 5 minutes

16. Treatment  Antitoxin- inactivates botulinum toxin which has not already attached to neurons. Most effective if given soon after exposure  Gastric Lavage- flush the GI tract of all possible toxin producing bacteria  Respiratory Support

17. Results  Throughout our research we determined prevention techniques to avoid botulism  We learned that Botulinum is a very powerful neurotoxin  Medicinal uses of Botulinum are very extensive and serve a large facet of conditions  Cosmetic uses also seem to be very valuable and currently seem to show little negative effects

18. Conclusion  Under strict control Botulinum seems to be very useful in the medical field and should continue to be used when necessary  Possible further studies include long term effects of continual Botulinum injections

19. Literature Cited  Erbguth, F. 2008. From poison to remedy: the chequered history of botulinum toxin. Journal of Neural Transmissions 115:559-565.  Oates, A. and J. Jankovic. 1991. Therapeutic uses of Botulinum Toxin. The New England Journal of Medicine 324: 1186-1194.  Simpson, L. 2004. Identification of the major steps in the botulinum toxin action. Annual Review of Pharmacology and Toxicology 44:167-193.  Simpson, L. 1981. The origin, structure and pharmacological activity of botulinum toxin. The American Society for Pharmacology and Experimental Therapeutics 33: 157-187.