Prions in the brain eliminated by homing molecules

biologynews.net ^ | April 24, 2012 | NA

[neverdem]

Toxic prions in the brain can be detected with self-illuminating polymers. The originators, at Linköping University in Sweden, has now shown that the same molecules can also render the prions harmless, and potentially cure fatal nerve-destroying illnesses.

Linköping researchers and their colleagues at the University Hospital in Zürich tested the luminescent conjugated polymers, or LCPs, on tissue sections from the brains of mice that had been infected with prions. The results show that the number of prions, as well as their toxicity and infectibility, decreased drastically. This is the first time anyone has been able to demonstrate the possibility of treating illnesses such as mad cow disease and Creutzfeldt-Jacobs with LCP molecules.

"When we see this effect on prion infections, we believe the same approach could work on Alzheimer's disease as well," says Peter Nilsson, researcher in Bioorganic Chemistry funded by ERC, the European Research Council.

Along with professors Per Hammarström and Adriano Aguzzi and others, he is now publishing the results in The Journal of Biological Chemistry.

Prions are diseased forms of normally occurring proteins in the brain. When they clump together in large aggregates, nerve cells in the surrounding area are affected, which leads to serious brain damage and a quick death. Prion illnesses can be inherited, occur spontaneously or through infection, for example through infected meat – as was the case with mad cow disease.

The course of the illness is relentless when the prions fall to pieces and replicate at an exponential rate. When researchers inserted the LCP molecules into their model system, the replication was arrested, possible through stabilizing the prion aggregates.

The variable components in an LCP are various chemical subgroups attached onto the polymer. In the published study, eight different substances were tested, and all of them had significant effect on the toxicity of the prions.

"Based on these results, we can now customise entirely new molecules with potentially even better effect. These are now being tested on animal models," Nilsson says.

Researchers want to go even further and test whether the molecules will function on fruit flies with an Alzheimer's-like nerve disorder. Alzheimer's is caused by what is known as amyloid plaque, which has a similar but slower course than prion diseases. Source : Linköping University

[neverdem]

Prion strain discrimination using luminescent conjugated polymers earlier work

Polythiophenes inhibit prion propagation by stabilizing PrP aggregates

The left sidebar is supposed to link a FReebie PDF. I didn't try it yet.

[neverdem]

Ping

[cripplecreek]

Prions, the lesser known first cousin of the moron.

[tired&retired]

Thank you for posting. This is excellent research. One step closer to understanding prions.

Questions from a novice:

“What causes the proteins to fold, replicate and become prions if there is no DNA, or RNA?” Another enzyme?

“Why is PrP so structurally sound and resistant to protease enzyme destruction?” Heat at 600 degree C., Boiling water, radiation .... Wow..

I find the research this past year showing how the lichen Parmelia sulcata when consumed by deer, elk and moose denature the prions in chronic wasting disease in the wild. Is is possible that the solution to denaturing prions is with fungal prions that do not affect humans? If PrPc is necessary for long term potentiation in the hippocampus and the variations of PrPsc block potentiation by creating amyloid plaques, the firewall to block Alzheimer’s just might be found in lichen prion research.

Natural Born Prion Killers: Lichens Degrade “Mad Cow” Related Brain Pathogen
By Philip Yam | May 19, 2011
http://blogs.scientificamerican.com/observations/2011/05/19/natural-born-prion-killers-lichens-degrade-mad-cow-related-brain-pathogen/?print=true

Too bad I’m over the hill. I would love to return to the university for a degree in microbiology/biochemistry. This stuff sure beats crossword puzzles! I find the whole field of epigenetic research and all of its sub fields absolutely fascinating.

[VRW Conspirator]

I>Prions in the brain eliminated by homing molecules

No, I do not want to watch "Brokeback Mountain" with you.

[aberaussie]

I would love to know more about this and CJD. A friend of mine died last week from this disease and there just doesn’t seem to be much out there on how one gets it and there is no cure. We watched my friend in her early 50’s go from her normal, active self to passing away in a matter of about six weeks.

[Ruy Dias de Bivar]

**** has now shown that the same molecules can also render the prions harmless, and potentially cure fatal nerve-destroying illnesses.***

So there is potential hope for liberals?

[exDemMom]

“What causes the proteins to fold, replicate and become prions if there is no DNA, or RNA?” Another enzyme?

The normally shaped proteins are produced routinely as part of the organism's normal function. I believe that what happens is that the misfolded prion interacts with the normally folded protein and causes it to refold in an abnormal manner. The newly abnormally folded protein then goes on to induce other normally folded proteins to change to a misfolded conformation. It has an exponential effect.

“Why is PrP so structurally sound and resistant to protease enzyme destruction?” Heat at 600 degree C., Boiling water, radiation .... Wow..

There are a couple of possibilities that might make prions resistant to degradation by proteases. One would be that the ubiquitination sites contained in all proteins are masked when the prion is misfolded. Ubiquitin is a small protein that recognizes and attaches to a specific amino acid sequence in a protein. That ubiquitin tag tells the protein to go to the proteasome, where it is degraded. Normally, ubiquitin recognizes and tags misfolded proteins.

The other possibility is that the prions are ubiquitinated normally, but the protease binding sites are masked, so the proteases cannot cleave the prions.

Without doing more reading, I cannot say if either or both of those mechanisms are protecting prions from degradation. But those are my educated guesses as to what may be going on.

As for prions being resistant to other processes that often destroy proteins--not all proteins are susceptible to all denaturing processes. It is actually not uncommon for proteins to survive boiling, for example. It's just that prions incorporate more features rendering them resistant to destruction than we observe in the vast majority of proteins.

[Weirdad]

Thanks for the interesting post.

[tired&retired]

Thank you for taking the time to answer my questions. As usual, answers lead to more questions! I’ll be doing some reading and research to take it further. Two of my children are performing cloning and genetic engineering in medical schools, but they no longer live at home. I miss having them here to answer my questions.

[exDemMom]

You’re welcome! I’m always happy to answer questions, if I know the answers. :D