Navigation Links
Scripps Research Institute scientists show copper facilitates prion disease

LA JOLLA, CA, August 9, 2012 Many of us are familiar with prion disease from its most startling and unusual incarnationsthe outbreaks of "mad cow" disease (bovine spongiform encephalopathy) that created a crisis in the global beef industry. Or the strange story of Kuru, a fatal illness affecting a tribe in Papua New Guinea known for its cannibalism. Both are forms of prion disease, caused by the abnormal folding of a protein and resulting in progressive neurodegeneration and death.

While exactly how the protein malfunctions has been shrouded in mystery, scientists at The Scripps Research Institute now report in the journal Proceedings of the National Academy of Sciences (PNAS) that reducing copper in the body delays the onset of disease. Mice lacking a copper-transport gene lived significantly longer when infected with a prion disease than did normal mice.

"This conclusively shows that copper plays a role in the misfolding of the protein, but is not essential to that misfolding," said Scripps Research Professor Michael Oldstone, who led the new study.

"We've known for many years that prion proteins bind copper," said Scripps Research graduate student Owen Siggs, first author of the paper with former Oldstone lab member Justin Cruite. "But what scientists couldn't agree on was whether this was a good thing or a bad thing during prion disease. By creating a mutation in mice that lowers the amount of circulating copper by 60 percent, we've shown that reducing copper can delay the onset of prion disease."

Zombie Proteins

Unlike most infections, which are caused by bacteria, viruses, or parasites, prion disease stems from the dysfunction of a naturally occurring protein.

"We all contain a normal prion protein, and when that's converted to an abnormal prion protein, you get a chronic nervous system disease," said Oldstone. "That occurs genetically (spontaneously in some people) or is acquired by passage 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 later at 180 days.

Researchers also found less abnormal prion protein in the brains of mutant mice than in control mice, indicating that copper contributed to the conversion of the normal prion protein to the abnormal disease form. However, all the mice eventually died from disease.

Oldstone and Siggs note the study does not advocate for copper depletion as a therapy, at least not on its own. However, the work does pave the way for learning more about copper function in the body and the biochemical workings of prion disease.

Contact: Mika Ono
Scripps Research Institute

Related biology news :

1. Scripps Research discoveries lead to newly approved drug for infant respiratory distress syndrome
2. Scripps Research Institute scientists find promising vaccine targets on hepatitis C virus
3. Scripps Research Institute Professor Gerald F. Joyce elected to American Academy of Arts & Sciences
4. Scripps Research Institute scientists develop antidote for cocaine overdose
5. Scientist wins $3 million renewal of one of longest-running NIH grants to Scripps Research
6. Scripps research scientists find anticonvulsant drug helps marijuana smokers kick the habit
7. Scripps Florida scientist awarded $1.5 million to design therapeutics with new RNA approach
8. Scripps Florida scientists identify neurotranmitters that lead to forgetting
9. Plastic trash altering ocean habitats, Scripps study shows
10. Scripps Florida scientists awarded $8.4 million grant to develop new anti-smoking treatments
11. Esther B. OKeeffe Foundation gives $2 million to the Scripps Research Institute
Post Your Comments:
Related Image:
Scripps Research Institute scientists show copper facilitates prion disease
(Date:6/2/2016)... , June 2, 2016 The Department ... has awarded the 44 million US Dollar project, for the ... Vehicle Plates including Personalization, Enrolment, and IT Infrastructure , ... in the production and implementation of Identity Management Solutions. Numerous ... however Decatur was selected for the ...
(Date:5/24/2016)... Ampronix facilitates superior patient care by providing unparalleled technology to leaders of the medical ... premium product recently added to the range of products distributed by Ampronix. ... ... ... Ampronix News ...
(Date:5/9/2016)... 2016 Elevay is currently known ... freedom for high net worth professionals seeking travel for ... connected world, there is still no substitute for a ... sealing your deal with a firm handshake. This is ... advantage of citizenship via investment programs like those offered ...
Breaking Biology News(10 mins):
(Date:6/24/2016)... TOKYO , June 24, 2016  Regular discussions on ... to take place between the two entities said Poloz. ... in Ottawa , he pointed to the ... and the federal government. ... Poloz said, "Both institutions have common economic goals, why not ...
(Date:6/24/2016)... ... June 24, 2016 , ... While the majority of commercial spectrophotometers and ... and the 6000i models are higher end machines that use the more unconventional z-dimension ... light beam from the bottom of the cuvette holder. , FireflySci has developed ...
(Date:6/23/2016)... ... June 23, 2016 , ... ... of its second eBook, “Clinical Trials Patient Recruitment and Retention Tips.” Partnering with ... in this eBook by providing practical tips, tools, and strategies for clinical researchers. ...
(Date:6/23/2016)... June 23, 2016   Boston Biomedical , ... compounds designed to target cancer stemness pathways, announced ... granted Orphan Drug Designation from the U.S. Food ... gastric cancer, including gastroesophageal junction (GEJ) cancer. Napabucasin ... to inhibit cancer stemness pathways by targeting STAT3, ...
Breaking Biology Technology: