Recombinant human prion protein inhibits prion propagation

October 9, 2013

Case Western Reserve University researchers today published findings that point to a promising discovery for the treatment and prevention of prion diseases, rare neurodegenerative disorders that are always fatal. The researchers discovered that recombinant human prion protein stops the propagation of prions, the infectious pathogens that cause the diseases.

"This is the very first time recombinant protein has been shown to inhibit diseased human prions," said Wen-Quan Zou, MD, PhD, senior author of the study and associate professor of pathology and neurology at Case Western Reserve School of Medicine.

Recombinant human is generated in E. coli bacteria and it has the same protein sequence as normal human brain protein. But different in that, the recombinant protein lacks attached sugars and lipids. In the study, published online in Scientific Reports, researchers used a method called protein misfolding cyclic amplification which, in a test-tube, mimics the prions' replication within the human brain. The propagation of human prions was completely inhibited when the recombinant protein was added into the test-tube. The researchers found that the inhibition is dose-dependent and highly specific in responding to the human-form of the recombinant protein, as compared to recombinant mouse and bovine prion proteins. They demonstrated that the recombinant protein works not only in the cell-free model but also in cultured cells, which are the first steps of translational research. Further, since the recombinant protein has an identical sequence to the , the application of the recombinant protein is less likely to cause side effects.

Prion diseases are a group of fatal transmissible brain diseases affecting both humans and animals. Prions are formed through a structural change of a normal prion protein that resides in all humans. Once formed, they continue to recruit other normal prion protein and finally cause spongiform-like damage in the brain. Currently, the diseases have no cure.

Previous outbreaks of mad cow disease and subsequent occurrences of the human form, variant Creutzfeldt–Jakob disease, have garnered a great deal of public attention. The fear of future outbreaks makes the search for successful interventions all the more urgent.

Zou, who also serves as the associate director of the National Prion Disease Pathology Surveillance Center at Case Western Reserve, and collaborators hope to extend their finding using transgenic mice expressing the human and patient-specific induced pluripotent stem cells (iPSCs)-derived neurons because they are made from human cells, offering an additional level of authenticity. The new animal models were generated in collaboration with Case Western Reserve School of Medicine faculty members, Robert Petersen, PhD, and Qingzhong Kong, PhD, who are the co-authors in this study. Further, patient-specific iPSCs-derived neurons have also just been generated in collaboration with fellow faculty, Paul Tesar, PhD, and Xin Qi, PhD.

Explore further: New approach to protecting prion protein from altering shape

Related Stories

New approach to protecting prion protein from altering shape

July 18, 2013

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 ...

The flexible tail of the prion protein poisons brain cells

July 31, 2013

For decades, there has been no answer to the question of why the altered prion protein is poisonous to brain cells. Neuropathologists from the University of Zurich and University Hospital Zurich have now shown that it is ...

Prion-like proteins drive several diseases of aging

September 5, 2013

Two leading neurology researchers have proposed a theory that could unify scientists' thinking about several neurodegenerative diseases and suggest therapeutic strategies to combat them.

Recommended for you

Artificial beta cells

December 8, 2016

Researchers led by ETH Professor Martin Fussenegger at the Department of Biosystems Science and Engineering (D-BSSE) in Basel have produced artificial beta cells using a straightforward engineering approach.

Key regulator of bone development identified

December 8, 2016

Loss of a key protein leads to defects in skeletal development including reduced bone density and a shortening of the fingers and toes—a condition known as brachydactyly. The discovery was made by researchers at Penn State ...

Researchers question lifelong immunity to toxoplasmosis

December 8, 2016

Medical students are taught that once infected with Toxoplasma gondii—the "cat parasite"—then you're protected from reinfection for the rest of your life. This dogma should be questioned, argue researchers in an Opinion ...

TET proteins drive early neurogenesis

December 7, 2016

The fate of stem cells is determined by series of choices that sequentially narrow their available options until stem cells' offspring have found their station and purpose in the body. Their decisions are guided in part by ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.