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 Six-legged livestock -- sustainable food production
11.05.2017 | Faculty of Science - University of Copenhagen

nachricht Elephant Herpes: Super-Shedders Endanger Young Animals
04.05.2017 | Universität Zürich

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: Can the immune system be boosted against Staphylococcus aureus by delivery of messenger RNA?

Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.

Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

How herpesviruses win the footrace against the immune system

26.05.2017 | Life Sciences

Water forms 'spine of hydration' around DNA, group finds

26.05.2017 | Life Sciences

First Juno science results supported by University of Leicester's Jupiter 'forecast'

26.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>