Featured Research

from universities, journals, and other organizations

New approach to protecting prion protein from altering shape, becoming infectious

Date:
July 18, 2013
Source:
Case Western Reserve University
Summary:
Scientists have identified a mechanism that can prevent the normal prion protein from changing its molecular shape into the abnormal form responsible for neurodegenerative diseases.

A team of researchers from Case Western Reserve University School of Medicine have identified a mechanism that can prevent the normal prion protein from changing its molecular shape into the abnormal form responsible for neurodegenerative diseases. This finding, published in the July 18 issue of Cell Reports, offers new hope in the battle against a foe that until now has always proved fatal.

Prion diseases include Creuzfeldt-Jakob disease and fatal familial insomnia. Unlike other transmissible diseases, the infectious agent is not a virus or bacteria, but an abnormally shaped prion protein. Scientists believe it self-replicates by binding to normal prion proteins and forcing them to change shape to become an abnormal, and thus diseased, protein.

"Once heretical, the notion that proteins alone can act as self-propagating infectious agent is now becoming accepted as a new paradigm in biology and medicine. However, the mechanism by which prion protein changes its shape remains largely unknown and highly controversial, hindering efforts to develop drugs for prion diseases," said Witold Surewicz, PhD, professor of physiology and biophysics and senior author of the study. "A heated debate continues as to which part of the prion protein undergoes the change and what is the three-dimensional structure of the infectious form of the protein."

The researchers generated a variant of prion protein designed to stabilize the normal shape of one specific part of the protein. They accomplished this goal by replacing just one out of more than 200 amino acid residues, the building blocks of the protein. In a series of experiments, the researchers found that the modified prion protein was highly resistant to changing its shape. In other words, this approach may be successful in blocking the coercive action of the abnormal prion protein.

The team then created transgenic mice that produced this "superstable" human prion protein and infected them with Creutzfeldt-Jakob disease prions. The mice did eventually develop symptoms, but the signs did not emerge for more than a year -- in fact, it took about 400 days. In contrast, mice without the modified prion protein showed symptoms within 260 days.

"Our discovery that a tailor-made mutation in one specific region of prion protein can prevent it from changing shape to a disease-associated conformation helps resolve the ongoing major controversy in the field regarding the mechanism by which infectious prions self-replicate," said Qingzhong Kong, PhD, associate professor of pathology and first author on the paper.

With no effective treatments currently available for these fatal diseases, this finding has also important implications for the development of new drugs. It suggests a novel pharmacologic strategy in which scientists can either identify or design a molecule that binds to prion protein and stabilizes its normal shape, thereby preventing propagation of the disease.

The study is a result of a collaborative effort between the laboratories of Surewicz, Kong, Pierluigi Gambetti, MD, professor of pathology at Case Western Reserve School of Medicine, and Frank Sφnnichsen, PhD, professor at the University of Kiel in Germany.

The study was supported by National Institute of Neurological Disorders and Stroke and National Institute of Aging grants including: NSO44158, NS038604, NS052319, and AG014359.


Story Source:

The above story is based on materials provided by Case Western Reserve University. Note: Materials may be edited for content and length.


Journal Reference:

  1. Qingzhong Kong, Jeffrey L. Mills, Bishwajit Kundu, Xinyi Li, Liuting Qing, Krystyna Surewicz, Ignazio Cali, Shenghai Huang, Mengjie Zheng, Wieslaw Swietnicki et al. Thermodynamic Stabilization of the Folded Domain of Prion Protein Inhibits Prion Infection in Vivo. Cell Reports, 18 July 2013 DOI: 10.1016/j.celrep.2013.06.030

Cite This Page:

Case Western Reserve University. "New approach to protecting prion protein from altering shape, becoming infectious." ScienceDaily. ScienceDaily, 18 July 2013. <www.sciencedaily.com/releases/2013/07/130718130454.htm>.
Case Western Reserve University. (2013, July 18). New approach to protecting prion protein from altering shape, becoming infectious. ScienceDaily. Retrieved April 16, 2014 from www.sciencedaily.com/releases/2013/07/130718130454.htm
Case Western Reserve University. "New approach to protecting prion protein from altering shape, becoming infectious." ScienceDaily. www.sciencedaily.com/releases/2013/07/130718130454.htm (accessed April 16, 2014).

Share This



More Mind & Brain News

Wednesday, April 16, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Are School Dress Codes Too Strict?

Are School Dress Codes Too Strict?

AP (Apr. 16, 2014) — Pushing the limits on style and self-expression is a rite of passage for teens and even younger kids. How far should schools go with their dress codes? The courts have sided with schools in an era when school safety is paramount. (April 16) Video provided by AP
Powered by NewsLook.com
Could Even Casual Marijuana Use Alter Your Brain?

Could Even Casual Marijuana Use Alter Your Brain?

Newsy (Apr. 16, 2014) — A new study conducted by researchers at Northwestern and Harvard suggests even casual marijuana use can alter your brain. Video provided by Newsy
Powered by NewsLook.com
Couples Who Sleep Less Than An Inch Apart Might Be Happiest

Couples Who Sleep Less Than An Inch Apart Might Be Happiest

Newsy (Apr. 16, 2014) — A new study by British researchers suggests couples' sleeping positions might reflect their happiness. Video provided by Newsy
Powered by NewsLook.com
Cognitive Function: Is It All Downhill From Age 24?

Cognitive Function: Is It All Downhill From Age 24?

Newsy (Apr. 15, 2014) — A new study out of Canada says cognitive motor performance begins deteriorating around age 24. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins