Dog prions could help develop therapies to fight prion diseases in humans

2020-01-17T17:09:15+01:00January 17, 2020|

A team of researchers from IRTA-CReSA and CIC BioGUNE has identified the mechanism that prevents dogs from developing prion diseases when exposed to these pathogens. It is a protein that offers them resistance, so imitating their functions in human proteins could have therapeutic applications.

Sierra Espinar and Dr. Enric Vidal, at the PRIOCAT laboratory of IRTA-CReSA.

Pigs, rabbits, horses and dogs are some mammals that have never suffered any prion disease naturally. Specifically, the dog is the most resistant animal species to these pathogens, but so far no transgenic model has been developed to prove it. A study led by the Center for Research in Animal Health (IRTA-CReSA) and the Centro de Investigación Cooperativa en Biociencias (CIC BioGUNE) published this week in The FASEB Journal has identified the protein responsible for the resistance of dogs to prion diseases

The work, carried out with transgenic mice that mimicked a dog’s organism, demonstrates that the key is in a region of the dog’s prion protein, specifically the position of one of the amino acids that make it up. «Now we know which amino acid is responsible for prion resistance; The next step will be to understand its operation. In this way, if we were able to imitate these same functions in people’s prion protein, we could develop therapies to combat prion diseases such as Creutzfeldt-Jakob syndrome, ”explains Dr. Enric Vidal, researcher at the Animal Health program IRTA at the IRTA-CReSA center.

One of the possible therapeutic strategies could be to block the misfolding of prions and prevent a neurodegenerative disease from developing.In this line, the study will also help solve one of the puzzles most persecuted by experts: knowing which molecular mechanism controls the bad folding of prions. «All mammals are susceptible to prion diseases that all have the prion protein. When it folds in the wrong way, it causes those around it to do it too and this is what can lead to fatal neurodegenerative diseases, still today without any treatment,” explains Vidal.

Living with prions, an evolutionary strategy of dogs?

Since the “mad cow disease” crisis, it is known that prions can be transmitted between different species, for example, through the consumption of meat contaminated with prions. The study has shown that two amino acids present in the dog’s prion protein, aspartic acid and glutamic acid, are exclusive to the canid family (dogs, wolves, foxes, coyotes, etc.). “A possible explanation of the resistance of dogs in prion diseases would be an evolutionary adaptation to the consumption of meat and carrion from their ancestors,” concludes Dr. Joaquín Castilla, researcher at CIC BioGUNE.

Part of the experiments in this study have been It was able to carry out thanks to the IRTA-CReSA Biocontainment Unit that forms the High Biological Safety Laboratory Network (RLASB), a Singular Scientific and Technical Infrastructure of Spain (ICTS), which allows working with high pathogenic agents under conditions Level 3 Biosafety.

This work was funded by two Spanish research projects, (AGL2015-65046-C2-1-R (JC) and AGL2008-05296-C02 (EV and BP)) (MINECO / FEDER), and the Interreg grant (POCTEFA EFA148 / 16). IRTA has the support of the CERCA / Generalitat de Catalunya Program.

Article:

Vidal E, Fernández-Borges N, Eraña H, et al. Dogs are resistant to prion infection, due to the presence of asparagine at position 163 of their prion protein. The FASEB Journal. 2020;00: 1–14. https ://doi.org/10.1096/fj.20190 2646R