Prions

John Cherwonogrodzky jcherwon at dres.dnd.ca
Fri Dec 9 16:48:03 EST 1994


Dear Colleagues:
     The subject of prions has come up and I think it is a very important 
topic. If you look at the history of disease outbreaks in the 20th century, 
there has been an intense see-saw between these and humans. (as G.P. Youmans 
et al. said in his book, 1975, "Although man can build a better mouse tra, 
nayure always seems to build a better mouse")

          -before 1928, 1/3 of people die to Gram-positive infections
- Fleming "discovers" (some evidence the guy was brilliant, not a bumbler)  
penicillin

          -Gram-negatives surface to cause most infections
- a wide range of antibiotics is found or created

          - Viruses, parasitic bacteria surface to become difficult to treat
- New anti-virals, liposomal formulations to transport antibiotics into cells
  are being developed

          - Alzheimer's, "mad cow's" disease, etc. appear to be the "tip of 
            the iceberg" of controversial Prion infections

Prions are not my expertise, but what I've read in the past implies that 
thereare 2 schools of thought. One is that prions are infectious protein 
particles, not having associated DNA/RNA (evidence is sensitivity to 
proteases, insensitivity to nucleases), the other is prions are a name for 
something no-one has a clue about.

     For the first, related topics are the view that life started on earth by 
the formation of replicating proteins. Bacterial spore proteins which get 
produced in the presence of chloramphenicol seems to be a throw-back to this 
principle. In another concept, a protein that acts like a promoter or a 
derepressor for the expression of a gene already coding for this same protein, 
could take over a cell's energies just like a virus. A third view of 
reverse-translatase, whereby DNA to RNA to protein goes the other way has 
never been observed and the cell's machinery isn't set up for this (a twist 
could be Chatelier's principle whereby an equilibrium can be forced the other 
way, or if catalysts can trap rare transitional reactions)
      
For the second, even sensitive RNA can become tougher if they have a chance to 
form hair-pins and some enzymes can be pushed to hydrolyze other compounds. 
Might a prion be a nucleic acid that is sensitive to the side reactions of 
proteases? If it was a short snip of infectious naked RNA or DNA, it would be 
almost impossible to find in all the other nucleic acid bits floating around 
in the cell.

     I'll stop here as I'm already out of my depth....John



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