Navigation Links
Variant prion protein causes infection but no symptoms

Abnormal prion proteins are little understood disease agents involved in causing horrific brain-wasting diseases such as Creutzfeldt-Jacob disease in people, mad cow disease in cattle and chronic wasting disease in deer and elk. Now, new research suggests that a variant form of abnormal prion protein--one lacking an "anchor" into the cell membrane--may be unable to signal cells to start the lethal disease process, according to scientists at the Rocky Mountain Laboratories (RML), part of the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health.

"This work provides novel insights into how prion and other neurodegenerative diseases develop and it provides tantalizing clues as to how we might delay or even prevent such diseases by preventing certain cellular interactions," notes NIAID Director Anthony S. Fauci, M.D. A paper describing the research was released online today by the journal Science. RML virologist Bruce Chesebro, M.D., directed the project. Other key co-authors from the Hamilton, MT, RML laboratory include Richard Race, D.V.M., and Gerald Baron, Ph.D. Their collaborators included Michael Oldstone, M.D., and Matthew Trifilo, Ph.D., of The Scripps Research Institute in La Jolla, CA, and Eliezer Masliah, M.D., of the University of California, San Diego (UCSD).

Drawing on experimental concepts first developed at RML a decade ago, the research team exposed two groups of 6-week-old mice to different strains of the agent that causes scrapie, a brain-wasting disease of sheep. Within 150 days of being inoculated with the natural form of scrapie prion protein, all 70 mice in the control group showed visible signs of infection: twitching, emaciation and poor coordination. In contrast, the scientists observed 128 transgenic mice--those engineered to produce prion protein without a glycophosphoinositol (GPI) cell membrane anchor--for 500 to 600 days and saw no signs of scrapie disease. Subsequent electron mic roscopic examinations at UCSD, however, confirmed that they produced amyloid fibrils, an abnormal form of prion protein, and that they even had brain lesions. More remarkably, according to Dr. Chesebro, the diseased brain tissue resembled that found in Alzheimer's disease rather than in scrapie.

Chesebro mentions two theories as to why the transgenic mice did not show symptoms of illness despite being infected:

* The host cell might require the GPI anchor to receive the "toxic signal" from the abnormal prion protein
* The plaques might be less toxic than the non-plaque form of prion protein clumps

In either case, more time might be required to produce disease due to the reduced toxicity, Dr. Chesebro says.

"There was so much about this research that surprised us and gave us ideas to pursue," says Dr. Chesebro. "First, the mice didn't get sick. That's very significant. Second, the dense accumulations of scrapie plaque in the brain resembled the plaque seen in Alzheimer's, but it wasn't toxic," which might support more recent concepts about plaque in Alzheimer's patients. "Previously, most researchers thought plaques were the toxic component of Alzheimer's that kills neurons, and many treatments focus on removing the plaques. But what if the plaques are inert, as they were in this research? What if only small clumps are toxic?"

If this hypothesis proves correct, Dr. Chesebro says, the ongoing research could eventually alter scientists' views on preventing prion diseases, shifting emphasis away from stopping the production of prion protein clumps and toward preventing interactions with prion protein anchored to cells, or learning to direct abnormal prion protein accumulations to specific parts of the brain where they will not produce symptoms.

"Abnormal prion protein by itself may not be rapidly lethal--in these mice it wasn't," Dr. Chesebro says.



Related biology news :

1. Strongest proof yet found for prion hypothesis
2. First technology to remove prions that cause vCJD from blood launched
3. Research into how prions act in the brain could hold the key to defeating diseases
4. Unweaving amyloid fibers to solve prion puzzles
5. New results validating Pall prion reduction filter disclosed at ISBT Congress
6. New evidence questions the simple link between prion proteins and madcow disease
7. Soil-bound prions that cause CWD remain infectious
8. Brittle prions are more infectious
9. Brown team finds crucial protein role in deadly prion spread
10. Scripps research study reveals structural dynamics of single prion molecules
11. Scientists identify prions infectious secret
Post Your Comments:

(Date:11/19/2015)... VIEW, Calif. , Nov. 19, 2015  Based ... market, Frost & Sullivan recognizes BIO-key with the 2015 ... Leadership. Each year, Frost & Sullivan presents this award ... product line catering to the needs of the market ... the product line meets and expands on customer base ...
(Date:11/17/2015)... , November 17, 2015 Paris ... 2015.   --> Paris from 17 ... DERMALOG, the biometrics innovation leader, has invented the first ... fingerprints on the same scanning surface. Until now two different ... Now one scanner can capture both on the same ...
(Date:11/16/2015)... 2015  Synaptics Inc. (NASDAQ: SYNA ), ... announced expansion of its TDDI product portfolio with ... and display driver integration (TDDI) solutions designed to ... TDDI products add to the previously-announced TD4300 ... resolution), and TD4322 (FHD resolution) solutions. All four ...
Breaking Biology News(10 mins):
(Date:11/30/2015)... 1, 2015  An interventional radiology technique shows promise for ... results of a study being presented today at the annual ... (RSNA). --> ... by interventional radiologists as a way to stop bleeding in ... a means of treating obesity is new. Mubin ...
(Date:11/30/2015)... includes an MPP licen ... niversity , s Solid Drug Nanoparticle (SDN) Technology ; ... up through cost cuts of priority ... based anywhere in the world will have the right to make, use and distribute ... where licensees based anywhere in the world will have the right to make, use ...
(Date:11/30/2015)... 2015 Harvard Apparatus Regenerative Technology, Inc. ... developing bioengineered organ implants for life-threatening conditions, today ... NASDAQ Stock Market that it has regained compliance ... noted that as a result of the closing ... $1.00 per share for more than ten consecutive ...
(Date:11/30/2015)... Md. , Nov. 30, 2015 ... development company committed to the fostering and monetization ... the current and prospective initiatives designed to create ... Chief Executive Officer of Spherix. "Based on published ... future licensees exceeds $50 billion and Spherix will ...
Breaking Biology Technology: