Botulinum Toxin A

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Botulinum Toxin A

• Botox
• David Byon, Molly Daugherty, Valina Edmunds,
  Vincent Yaptinchay

http//www.dbtechno.com/images/botox.jpg
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What is it?

• Neurotoxin secretion from Clostridium botulinum
• LD50 is 1 nanogram per kilogram of body weight
  VERY POTENT
• One of the most poisonous naturally occurring
  substances in the world
• Used to treat a variety of other ailments
• Not just for cosmetic use

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How it works step by step

• Botulinum Toxin A (BT-A) enters by endocytosis
  into the presynaptic motor neuron
• The light chain of BT-A (the smaller of the two
  polypeptides in this protein) disassociates from
  the heavy chain in the endocytotic vesicle
• Light chain cleaves SNAP-25 (a membrane bound
  protein) on the presynaptic membrane
• - SNAP-25 necessary for fusing vesicle with
  presynaptic membrane for exocytosis
• Ach cannot be exocytosed
• New axon collaterals deliver Ach to muscle fiber
  or gland
• New production of SNAP-25 ?Ach can now be
  released
• Axon collaterals retract
• Normal function is restored

Silverthorn, D.U. (2007). Human physiology An
integrated approach 4th edition. San Francisco
Pearson, 274
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Normal vs. BT-A
http//kugi.kribb.re.kr/KUGI/Pathways/BioCarta/h_b
otulinPathway/h_botulinPathway.gif
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Affects of BT-A
No change
No change
No change
Decrease
No change
No change
Absent in at least some cells
Decrease
Decrease
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Other uses
Strabismus
Blepharospasm (orbicularis oculi)
Hyperhidrosis
www.orbis.org http//microbewiki.kenyon.edu/images
/e/ef/Botwoman.jpg http//www.sweathelp.org/Englis
h/images/Botox_injections.jpg http//www.cybersigh
t.org/bins/volume_page.asp?cid1-3-4-33
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Analogy

• Deer runs across freeway and causes car accidents
  and freeway becomes impassable
• Light chain cleaves SNAP-25 no exocytosis of
  Ach
• Cars further back on the freeway take local
  detours
• Axon collateral growth allows alternative
  exocytosis
• Deer decomposes on freeway. Cars travel freely.
• Snap-25 regrowth gt exocytosis of Ach
• People stop using local road detours
• Axon collateral recede

http//www.turbophoto.com/Deer-Photos/index.htm
http//www.mahoningcountyoh.gov/MahoningWeb/Meetin
gsandPublicNotices/RoadClosings.htm
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References

• Dressler, D. (2005). Botulinum Toxin Mechansism
  of Action. Retrieved April 25,
  2008 from http//content.karger.com/produktedb/pr
  odukte.asp?typfulltextfileENE2005053001003
• Skorin, L. (2004). Botulinum Toxin in Medical
  Therapy. Retrieved April 25, 2008 from
  http//www.revoptom.com/index.asp?page2_1213.htm
  
• Helveston, E. (1999). Botox For Blepharospasm and
  Strabismus. Retrieved April 25, 2008 from
  http//www.cybersight.org/bins/volume_page.asp?ci
  d1-3-4-33
• Harvard Womans Health Watch. (2003). Botox Not
  Just For Faces. Retrieved April 25, 2008 from
  http//web.ebscohost.com/ehost/delivery?vid3hid
  9sid6a9c9b
• Bellaire Neurology. (2005). Botulinum Toxin.
  Retrieved April 25, 2008 from http//www.loftusmd
  .com/Articles/botulinum/botulinum_toxin.html
• American Association for Pediatric Ophthalmology
  and Strabismus. (2001). Adult Strabismus General
  Information. Retrieved April 25, 2008 from
  http//www.aapos.org/display common.cfm?an5