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Scripps Research Institute scientists show copper facilitates prion disease

age of infectious prions. Passage can occur by eating infected meat; in the past, by cannibalism in the Fore population in New Guinea through the ingestion or smearing of infectious brains; or by introduction of infectious prions on surgical instruments or with medical products made from infected individuals."

When introduced into the body, the abnormal prion protein causes the misfolding of other, normal prion proteins, which then aggregate into plaques in the brain and nervous system, causing tremors, agitation, and failure of motor function, and leads invariably to death.

A Delicate Balance

The role of copper in prion disease had previously been studied using chelating drugs, which strip the metals from the bodyan imprecise technique. The new study, however, turned to animal models engineered in the lab of Nobel laureate Bruce Beutler while at The Scripps Research Institute. (Beutler is currently director of the Center for the Genetics of Host Defense at UT Southwestern.)

The Beutler lab had found mice with mutations disrupting copper-transporting enzyme ATP7A. The most copper-deficient mice died in utero or soon after birth, but those with milder deficiency were able to live normally.

"Copper is something we can't live without," said Siggs. "Like iron, zinc, and other metals, our bodies can't produce copper, so we absorb small amounts of it from our diet. Too little copper prevents these enzymes from working, but too much copper can also be toxic, so our body needs to maintain a fine balance. Genetic mutations like the one we describe here can disrupt this balance."

Death Delayed

In the new study, both mutant and normal mice were infected with Rocky Mountain Laboratory mouse scrapie, which causes a spongiform encephalopathy similar to mad cow disease. The control mice developed illness in about 160 days, while the mutant mice, lacking the copper-carrying gene, developed the disease la

Contact: Mika Ono
Scripps Research Institute

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