Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

A new twist on the mad cow

30.01.2004


Scientists at The Scripps Research Institute discover the normal prion protein may contribute directly to disease



In a surprising twist on a timely topic, scientists at The Scripps Research Institute are presenting evidence that mad cow disease prions cannot kill neurons on their own and that normal, healthy cellular prion protein may be a direct accomplice in unleashing neuronal destruction.

Bovine spongiform encephalopathy (BSE), or mad cow disease, is caused by prions, a misfolded "scrapie" form of the normal cellular protein, which is found on the surface of human, sheep, and cow neurons. Prion infections are also implicated in one form of the same disease in humans, called Variant Creutzfeldt-Jakob Disease, an incurable condition that causes neurologic abnormalities, dementia, and eventually death.


BSE has caused widespread public concern when it has appeared in cattle in Europe, Canada, and most recently the United States, as it is believed that the disease is transmitted across species by the consumption of prions from a diseased animal’s central nervous system.

Unlike most infectious diseases, the infectious material of mad cow and other prion disease is not a virus, bacteria, or some other pathogen, but a protein. Normally, prion proteins are expressed throughout the body and sit anchored onto the surfaces of cells in a wide variety of tissues, particularly on cells in neuronal tissue. They are something of an enigma because scientists do not know what they do there. But if the function of prions is mysterious, their malfunction is notorious.

"The prion protein," says Scripps Research investigator Anthony Williamson, Ph.D., "has a Jekyll and Hyde personality."

A New View of Normal Prions

Previously, scientists viewed the normal cellular prion protein as mere fodder that the scrapie prions would turn into more scrapie prions until an army of scrapies grew into a spongy mass, killing brain cells, and causing the neurological wasting that characterizes the disease.

Now, Williamson and his colleagues in the Department of Immunology at The Scripps Research Institute are telling another story.

In an upcoming issue of the journal Science, Williamson and his colleagues present evidence that scrapie prions cannot kill neurons on their own. They required normal cellular prions to be present.

Furthermore, Williamson and his colleagues discovered that they were able to induce catastrophic neurotoxicity in vivo without any scrapie prions at all by adding antibody molecules, which cross-linked the normal prion protein. Thus, engaging and activating the normal prion protein triggered the type of neurodegeneration that characterize BSE and variant Creutzfeldt-Jakob.

This suggests a possible mechanism for prion pathogenesis-- that scrapie prions cross-link normal cellular prions, killing neurons in the process. Rather than being innocent bystanders until converted into scrapie prions, normal cellular prions may be essential ingredients for prion diseases like BSE.

While illuminating the mechanisms of disease, the findings also suggest caution to one possible approach to fighting prion diseases-- administering antibodies or small molecules that will bind to the normal prion protein and prevent the scrapie prions from binding. However, it now appears that in cross-linking the normal prion protein, such a therapy may actually promote rapid spongiosis.


The research article, "Crosslinking Cellular Prion Protein Triggers Neuronal Apoptosis in vivo," is authored by Laura Solforosi, Jose R. Criado, Dorian B. McGavern, Sebastian Wirz, Manuel Sánchez-Alavez, Shuei Sugama, Lorraine A. DeGiorgio, Bruce T. Volpe, Erika Wiseman, Gil Abalos, Eliezer Masliah, Donald Gilden, Michael B. Oldstone, Bruno Conti, and R. Anthony Williamson and appears in Science Express on January 29, 2004. Science Express provides rapid electronic publication of selected papers in the journal Science. Print versions of these papers will appear in Science after several weeks. See: http://www.sciencemag.org/sciencexpress/recent.shtml.

The research was funded by the National Institutes of Health, the Department of Defense National Prion Research Program, and the Clark Fellowship in Neurophysiology from the Brain Research and Treatment Center, Scripps Clinic.

About The Scripps Research Institute

The Scripps Research Institute in La Jolla, California, is one of the world’s largest, private, non-profit biomedical research organizations. It stands at the forefront of basic biomedical science that seeks to comprehend the most fundamental processes of life. Scripps Research is internationally recognized for its research into immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune diseases, cardiovascular diseases and synthetic vaccine development.

Jason Bardi | Scripps
Further information:
http://www.sciencemag.org/sciencexpress/recent.shtml
http://www.scripps.edu/
http://www.scripps.edu/news/press/012904.html

More articles from Agricultural and Forestry Science:

nachricht Researchers discover a new link to fight billion-dollar threat to soybean production
14.02.2017 | University of Missouri-Columbia

nachricht Important to maintain a diversity of habitats in the sea
14.02.2017 | University of Gothenburg

All articles from Agricultural and Forestry Science >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Microhotplates for a smart gas sensor

22.02.2017 | Power and Electrical Engineering

Scientists unlock ability to generate new sensory hair cells

22.02.2017 | Life Sciences

Prediction: More gas-giants will be found orbiting Sun-like stars

22.02.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>