Well, it is -and should be hard to beleive- that a "protein-only" can serve as an infectious agent. It is little more than 20 years ago that I was asked to analyze the first prion-K.O. mice in Zürich, but I was a very SELF-determined young scientist and wanted to avoid just becoming second author of one or more expected Nature paper (with Charly Weissmann). I prefered to find a lab to work on any other K.O. - but unfortunately found the wrong lab in Karlsruhe...

OK, back to the question: there was a Nobel prize, I think in the 1990s by Stanley Prusiner in S.F. since he was fighting his "Protein-only hypothesis" - a decade long, heavily discussed hypothesis, later theory. It became clear by cloning of the Prion gene (in human and mammalian) that there is a cellular protein. Some families even carry mutations (GSS, Gerstmann-Sträussler-Scheinker syndrome, if I remember correctly).

Transferring prions from animals could infect other animals (but even I think in the 1960 the normal sterilization of brain surgery instruments could transfer the disease). Transgenic animal studies with mouse or hamster specific genes, but finally the K.O. mice which according to Charles Weissmann did not look less intelligent than the normal mice could support the prion-only hypothesis: those mice could not get infected, as far as I remember, only after transferring again a prion gene into them.

It was discussed why Weissmann did not get the Nobel prize, since he was more or less the first to support (or give a final proof to) the original theory with cloning and knocking out the gene, but the Nobel committee may have dediced that Prusiner fighted decades against most of the scientific community...

So, the infectious protein can obviously transfer the "wrong" conformation to the normal prion protein. But nowadays this field may be academically still very interesting, although it may not that relevant due to lack of human victims. It was expected that millions could die, since so many cows in Great Britain and some few in Switzerland in those years develeped BSE. Years later, some surprisingly young humans were killed by the "new variant" of Jacob-Creutzfeld disease which is terrible for the families, but the major epidemy was successfully avoided by killing millions of cows and current removal of the potential infectious major nervous system parts.

It is not that the prion protein replicates itself. We all have the native form of the prion protein in our brain. problems actually start when some of the prion proteins get misfolded into a form that aggregates (the infectious form), which also induces misfolding in the native protein, increasing the amount of aggregates, and inducing more and more of the native form to misfold.

You may want to go back further to Mid 50s to late 70s work of Dr. Carlton Gajdusek

http://www.theguardian.com/science/2009/feb/25/carleton-gajdusek-obituary

Although it was classified under "slow viruses" he had shown that the transmissible agent is unlikely to be a nucleic acid [based on X-radiation studies]. I had the fortune of knowing him and working with him for a short period. We looked into the role of free radicals in the formation of spongiform pathology in hamster scrapie model.

I believe there is more work to be done in this area as we still do not know the "precise molecular mechanism " of the induction of miss-folding. We developed some Prion specific DNA aptamers [7. Takemura K, Wang P, Vorberg I, Surewicz W, Priola SA, Kanthasamy A, Pottathil R, Chen SG, Sreevatsan S. DNA aptamers that bind to PrP(C) and not PrP(Sc) show sequence and structure specificity. Exp Biol Med (Maywood). 2006 Feb;231(2):204-14. Erratum in: Exp Biol Med (Maywood). 2006 Apr;231(4):485. PubMed PMID: 16446497]

More work needs to be done in the area of molecular basis of C to Sc transformation of prion proteins

When I evaluated the prion research as not that important, I thought about the hype 25 years ago, when everybody expected millions of deaths by eating hamburgers... Of course I am in favour of any basic research, and sometimes applied science as well, when it comes to major benefits for major parts of the society often paying for such research with tax money. But sometimes I think it is waste of money if there are more researchers paid for working on extremely rare diseases (like some types of tumors) when otherwise with the same amount of money some of the tumor types could be examined which appear thousands of times more often... So, I respect all prion researchers, although it is reasonable to expect not another Nobel prize in this field too soon.

EDIT: Interestingly, there are different alleles for the prion gene, and if I remember right, the young victims of the new variant of Creutzfeld-Jacob were homozygous for one of the alleles. It may just be that those proteins switch easier or faster into the wrong tertiary structure. Two of the wrong alleles increases the probability.

Although vCJD (the human disease associated with the consumption of tainted beef) is rare, with less than 200 cases worldwide, other prion diseases, such as sporadic CJD, are not as rare(although still relatively rare). But we should keep in mind that the research of prion diseases and the mechanism of plaque formation by proteins has helped us understanding several more common diseases such as ALS, Alzheimers, and other amyloid-related diseases.

Indeed, as Robert mentioned, the victims of vCJD have been MM genotype (codon 129). MV and VV genotype individuals are believed to have a much longer incubation time, or be immune to the disease,

Thanks, Patrick, for freshing up my memories on the genotypes, I didn't follow that topic during the last decade.

Why plant don't have any prions?

Now, I think I got it right: plants may not have "genuinely" prions, but at least some seem to be able to uptake animal prions and cause infection of mammalians (in north america). So, I am wondering if anything else (not yet identified) in plants can also augment the probability to change the conformation of human (or other mammalian or animal) prions. Does anyone know if vegeterians get more or less or different subtypes of Creutzfeld-Jacob disease?

So what make the plants unable to produce prions?..

Can anybody suggest me quality reference, where I could collect more detail about prions, their origin, biology, mechanism in vivo and replication!!

I do not accept the idea that plants are unable to produce prions. The problem is what does prion mean? If we look at the concept that some proteins may transform the conformation of other proteins of the same (but a little different) type, this may be also true for plants. I do not see why plants do not be capable of this type of molecular agregation. On the other hand, that plants do not share with animals their specific prion protein whose anomaly is responsible for the neurological disease is an evidence. Remember that some important concepts of biology where often long to be recognized in plants... Immunity, electric conduction of message, communication between plants or between plants and microbes or animals, are some examples.

Yep Herve, well said but Prions are observed in fungi which too eukaryote still lower to animals and plants in evolution hierarchy (i think), so why plants are exception, why no body says about plant prions (as i know) and do you have any sort of reference which reasoning this issue? And another problem, do Amyloids and prions are same, in many articles people do mixed up with these two things and finally I too messed up. Can some body make this clear to me??

For the easiest understanding, you may look for the genetic sequences of the proteins... There are Prion genes and there is for example an APP gene, of course different. I guess that after the hype of prion research around the Nobel prize in the mid-1990s there is not so much room for improvement and all those who did not have a chance to become professor in that time had to change their research field. So, I think there are not many opportunities for a career in such a field...

Please visit the following links/references for

Plants and prions [not sure if they are really plant origin or just carrier yet]

http://www.alzheimers-prions.com/pdf/PRIONSINPLANTSChristopherJohnson.pdf

http://www.wisconsinwatch.org/2013/09/27/prions-in-plants-new-concern-for-chronic-wasting-disease/

Cross species susceptibility

Transmission of prions between species is inefficient, and only a small proportion of exposed recipients become sick within their lifetimes. A new study takes a close look at one exception to this rule: bank voles appear to lack a species barrier for prion transmission, and their universal susceptibility turns out to be both informative and useful for the development of strategies to prevent prion transmission.

http://www.sciencedaily.com/releases/2014/04/140403212519.htm

Mechanism of Toxicity

Tiziana Sonati, Regina R. Reimann, Jeppe Falsig, Pravas Kumar Baral, Tracy O’Connor, Simone Hornemann, Sine Yaganoglu, Bei Li, Uli S. Herrmann, Barbara Wieland, Mridula Swayampakula, Muhammad Hafizur Rahman, Dipankar Das, Nat Kav, Roland Riek, Pawel P. Liberski, Michael N. G. James, and Adriano Aguzzi.The flexible tail of the prion protein mediates the toxicity of antiprion antibodies. Nature, July 31, 2013 DOI: 10.1038/nature12402

Anti-prion drugs

Y. Pang, S. Kurella, C. Voisset, D. Samanta, D. Banerjee, A. Schabe, C. Das Gupta, H. Galons, M. Blondel, S. Sanyal. The Antiprion Compound 6-Aminophenanthridine Inhibits the Protein Folding Activity of the Ribosome by Direct Competition. Journal of Biological Chemistry, 2013; 288 (26): 19081 DOI: 10.1074/jbc.M113.4667483

M. Zhou, G. Ottenberg, G. F. Sferrazza, C. Ida Lasmezas. Highly neurotoxic monomeric -helical prion protein. Proceedings of the National Academy of Sciences, 2012; DOI: 10.1073/pnas.1118090109

http://www.sciencedaily.com/releases/2009/08/090817184439.htm

Transmission C. Ligios, M. G. Cancedda, A. Carta, C. Santucciu, C. Maestrale, F. Demontis, M. Saba, C. Patta, J. C. DeMartini, A. Aguzzi, C. J. Sigurdson. Sheep with Scrapie and Mastitis Transmit Infectious Prions through the Milk. Journal of Virology, 2010; 85 (2): 1136 DOI: 10.1128/JVI.02022-10

Recent developments in Prion research are going to help our understandings beyond prion associated diseases.