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Scientists reveal how deadly toxin hijacks cells

Scientists have pinpointed exactly how botulinum neurotoxin A - a potential agent of biological warfare and one of the most lethal toxins known to man - is able to sneak into cells.

The finding is crucial for the development of new treatments against botulism, a paralytic illness caused by the toxin more commonly known as botox. As small amounts of botox are also known to alleviate many medical problems, the recent work could help to quell any risks associated with the toxin's clinical use.

Writing in the current online edition of Science, a team of researchers at the University of Wisconsin-Madison and the University of Texas report that botox latches onto a protein known as SV2 to gain entry into neurons.

"Our work shows that botox is really smart and clever," says senior author Edwin Chapman, a UW-Madison professor of physiology and an investigator of the Howard Hughes Medical Institute. "It uses SV2 to sneak into nerves like a Trojan horse."

"Botulinum neurotoxins are among the six most dangerous bioterrorism threats," adds lead author Min Dong, a UW-Madison postdoctoral researcher in the department of physiology. "Knowing the protein receptor for [botulinum toxins] can pave the way for developing anti-toxin reagents which may block the entry of toxins into cells."

The botulinum toxins, of which there are seven types, are made by a bacterium commonly found in soil, known as Clostridium botulinum. Of the seven-identified by the letters A through G--botox A lasts a particularly long time in neurons. While that feature makes it especially useful in the clinic, it also means that botox A may pose a particularly dangerous threat as a biological weapon.

The toxin enters neurons by binding to nerve endings and preventing the release of crucial chemical messengers, known as neurotransmitters, that communicate with muscles. When enough nerve endings are invaded, botox can lead to paralysis and death.

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Source:University of Wisconsin-Madison


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