Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Dartmouth study advances prion disease research

16.10.2003


Adding to the paradox of prion diseases, Dartmouth Medical School researchers have discovered that RNA plays a role in converting a normal prion protein into a mutant that leads to mad cow disease and other fatal brain illnesses.



Their study, reported in the Oct. 16 issue of Nature, provides important clues to understanding the role of prions, unorthodox infectious agents whose ability to transmit disease has confounded physicians and scientists. The work, by Dr. Surachai Supattapone, assistant professor of biochemistry and of medicine, opens new avenues of exploration for diagnosis and treatment of a perplexing group of neurodegenerative disorders called prion diseases.

Prions lack RNA or DNA, the nucleic acids that contain genetic information to replicate. No one knows what spurs conversion of a normal prion protein to a disease-causing counterpart. Supattapone, with coauthors Nathan Deleault and Ralf Lucassen, has discovered that RNA may be a catalyst for transformation.


"It has been well proven that nucleic acids, including RNA, are not part of the infectious agent, so it’s an ironic twist that a catalyst for the reaction may be RNA," said Supattapone. He emphasized, however, that the findings are consistent with the "protein-only" hypothesis of prion diseases because the nucleic acids are in the host and are not contained in the disease spreading particle.

Prions related to infectious brain diseases such as Cruetzfeld-Jakob disease in humans, chronic wasting or scrapie in animals have long been known, but these diseases often develop over years, so research to piece together the process has moved slowly.

The discovery more than a quarter century ago that prions were proteins, devoid of nucleic acids, upended what scientists assumed not only about disease transmission, but about life itself. All mammals have a gene to make a prion protein, but the normal prion is a different shape than the infectious prion. Somehow, this normal protein is modified into an abnormal counterpart that accumulates exponentially in the brain until death.

"It’s a curious thing, because this protein is able to stimulate its own formation and change, without nucleic acids. It’s been a fascinating question for people to come to grips with scientifically in addition to being the central reaction in an important medical problem," Supattapone said.

Now, his team has discovered that specific RNA molecules are required to transform prion proteins into their abnormal shapes. They devised a technique to observe how the normal prion protein, called PrPC, efficiently converts into the abnormal infectious protein, PrPSc (scrapie), in a test tube. This biochemical assay enabled the researchers to pinpoint the conversion mechanisms in the cell.

They found that adding enzymes that slice RNA blocked accumulation of abnormal prion protein. Taking it further, the researchers purified RNA and reconstituted the activity they had abolished with the RNA-cleaving enzymes. Adding enzyme knocked down scrapie protein and adding RNA brought it back up, indicating that RNA is really a stimulator. Moreover, RNA appears to boost the signal even of dilute amounts of scrapie protein.

The existence of RNA-converting factors could aid early detection of prion diseases, now incurable and invariably fatal. Ideal treatment time would be in the nascent stages of symptoms, before development of permanent brain damage. Current diagnosis requires a small brain biopsy, that may not provide much abnormal protein, but a technique where RNA can be added to amplify the signal may provide a more sensitive early diagnosis.

The next step is to pinpoint the RNA molecule, which seems to be only in mammals. "This stimulatory RNA appears to be a specific one, which makes it exciting to study. If we can identify, clone and produce this specific RNA, it may be useful as therapeutic target or a diagnostic tool. In addition, it may offer clues to the mechanism of conversion," Supattapone said. More studies are required to confirm the results in animals, he cautioned, but he is optimistic that the process in the test tube will contribute important insight into prion diseases.


The work was supported by the Burroughs Wellcome Fund Career Development Award, the Hitchcock Foundation and an NIH Clinical Investigator Development Award. For more information, contact Supattapone at: Surachai.Supattapone@dartmouth.edu or 603-650-1192.

Hali Wickner | EurekAlert!
Further information:
http://www.dartmouth.edu/

More articles from Studies and Analyses:

nachricht New study: How does Europe become a leading player for software and IT services?
03.04.2017 | Fraunhofer-Institut für System- und Innovationsforschung (ISI)

nachricht Reusable carbon nanotubes could be the water filter of the future, says RIT study
30.03.2017 | Rochester Institute of Technology

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

Im Focus: Quantum-physical Model System

Computer-assisted methods aid Heidelberg physicists in reproducing experiment with ultracold atoms

Two researchers at Heidelberg University have developed a model system that enables a better understanding of the processes in a quantum-physical experiment...

Im Focus: Glacier bacteria’s contribution to carbon cycling

Glaciers might seem rather inhospitable environments. However, they are home to a diverse and vibrant microbial community. It’s becoming increasingly clear that they play a bigger role in the carbon cycle than previously thought.

A new study, now published in the journal Nature Geoscience, shows how microbial communities in melting glaciers contribute to the Earth’s carbon cycle, a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

New quantum liquid crystals may play role in future of computers

21.04.2017 | Physics and Astronomy

A promising target for kidney fibrosis

21.04.2017 | Health and Medicine

Light rays from a supernova bent by the curvature of space-time around a galaxy

21.04.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>