- With its harsh chemicals and dense protective walls,
the digestive system mounts a formidable defense against food-borne invaders.
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- So how does the particle in tainted beef that causes
the human version of mad cow disease manage to get by unscathed?
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- It does what any good commando would -- it links up with
an escort that safely whisks it past the intestine's cellular sentries,
according to new research from Case Western Reserve University.
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- The study, published this week in the Journal of Neuroscience,
demonstrates for the first time a tactic that the infectious proteins known
as prions use to penetrate the digestive system's extensive security barriers.
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- Once past, they can gain access to the bloodstream and,
eventually, the central nervous system. There, dark gummy clusters of the
malformed prions render the human brain a sponge-like mess. There currently
is no prevention or cure.
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- Scientists say the study is intriguing and suggests possible
ways to block prions' stealthy entrance strategy.
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- "This is exactly the kind of thing we're hoping
to learn," said Michael Nunn, infectious diseases program director
at the National Institute for Neurological Disorders and Stroke, which
supported the Case research. "It's helping to unravel things in this
field that have long been mysterious."
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- "It's a good start for understanding how prions
travel in our body," added molecular biologist Giuseppe Legname, a
member of the University of California, San Francisco lab that originally
identified prions as the culprit in human and animal brain-wasting diseases
like mad cow. "This work opens up a new possible drug target for the
treatment of (prion) diseases."
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- About 150 people worldwide have died from eating beef
contaminated with mad cow prions. None of the cases is believed to have
originated in the United States, and the government regularly tests the
nation's beef supply. Public health officials still are concerned about
the disease's spread, and the emerging threat of prion disease in wild
deer and elk.
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- The human digestive system has elaborate -- though not
entirely foolproof -- measures to regulate the absorption of nourishment
and prevent the intake of harmful contaminants.
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- After stomach acids liquefy a meal, powerful enzymes
in the small intestine complete the breakdown of nutrients by chemically
scissoring up their long ribbons of protein molecules.
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- The intestines are lined with a mesh of protective cells.
They're tightly connected to prevent anything from crossing through to
the bloodstream without approval. Gatekeepers called receptors on the intestinal
cells' surface control entry and exit.
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- Until the Case study, scientists knew very little about
how the relatively large prions managed to circumvent these roadblocks.
"It's kind of amazing that, given the molecular mass of the (prion),
it would be able to go through because the intestine is very, very selective,"
said associate professor of pathology Dr. Neena Singh, who led the research.
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- So working in a biosafety lab, Singh's team set up a
model of the digestive process, using the same caustic chemicals and hothouse
temperatures present in the human gut.
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- Then they introduced samples of brain tissue from a man
who died of the kind of brain-wasting disease that prions cause, and watched
what happened.
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- Digestive enzymes slice most proteins to bits, but the
prions escaped with only a few nicks probably, Singh said, because their
misshapen folds shield most of their vulnerable spots.
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- Tests showed that the prions also made it past the cells
that Singh and her colleagues used to simulate the intestinal wall. The
researchers were surprised to see that the prions didn't cross the barrier
alone.
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- They had somehow joined with another protein called ferritin,
one that's present in abundance in a typical serving of beef. The human
body uses ferritin to store excess iron until it's needed. Because it's
a vital protein, it's on friendly terms with the intestine's sentry cells
and regularly gets passed through.
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- Apparently by piggybacking on ferritin, prions slip by
too, although the exact mechanism is still unknown. Singh said it's possible
prions take advantage of other, as yet undiscovered "carrier proteins"
similar to ferritin to foil the intestinal barrier.
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- Figuring out how to break up the ferritin-prion pairing
-- in essence, separating the wolf from its sheepskin -- might prevent
the mad cow protein from getting absorbed and starting on its lethal journey
to the brain. That's one of several avenues Singh and her team intend to
pursue.
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- "I think this is the first step toward our understanding
of (prion) transport," she said. "The major contribution is the
prevention of transport itself, so you never get the disease."
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- © 2004 The Plain Dealer.
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- http://www.cleveland.com/news/plaindealer/index.ssf?/base/news/
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