The proteasome disfunctions are implicated in complex syndromes like neurodegenerative diseases, which often involve accumulation of abnormally folded or misfolded proteins; for example the plaques and tangles of Alzheimer disease. It has been shown that prions are misfolded proteins responsible for Mad Cow disease. Normal proteins are tagged by ubiquitin subunits and dragged to the huge proteasome complexes for degradation. Can the reason for a misfolded protein to scape from degradation be that ubiquitin does not recognize a site on that protein to bind to? or because the ubiquitination has been altered in the cell? The idea is to tag the misfolded protein such as a prion with a target that can be recognized by ubiquitin and thus destroyed
before it start to accumulate and form plaques.
Anyone out there knows about research and papers published regarding ubiquitination and prions?

Here is a paper on Prion ubquitination:

Prion protein is ubiquitinated after developing protease resistance in the brains of scrapie-infected mice.

Kang SC, Brown DR, Whiteman M, Li R, Pan T, Perry G, Wisniewski T, Sy MS, Wong BS.

J Pathol. 2004 May;203(1):603-8.

Is it possible that the ubquitination machinery is just overwhelmed by protease resistant misfolded proteins in these diseases? If so your proposed tagging idea may still not be enough to rescue degradation. Certainly worth a shot though.

I found this quite interesting and a PubMed search turned up a bunch of papers: Science 2002, J. Alzheimers Dis 2003, J. Immunol 2004, and more - even came across a Newsweek article. Seems like many people are working on the protease aspects of prions.
Your idea would need a multimolecular complex - a) to recognize the sc or related variant prion proteins and b) to tag and target them.
Also, it is definitely possible that some cellular proteases are capable of cleaving of mutant/excess prions - not with great efficiency perhaps. I guess there should be more info in this field in the next 2-3 yrs going by my rather cursory reading of whats published.
Is anyone in the forum actually working on aspects of this - it would be great to have a first hand account.

This is a very interesting subject. What I don't understand is that a prion protein from a diseased meat gets into our digestive system and instead of being digested by the appropriate enzymes etc. goes into the blood stream and gets inside the cells?? Based on what we know about proteasomes and ubiquitination everything happens inside the cell before the protein is secreted so a misfolded protein accumulates inside the cell and causes cell stress and eventually plaques. How a misfolded protein-prion-comes from the outside gets into the cells of the central nervous system and then binds to and changes other normal proteins into misfolded proteins by changing their configuration. Is the cell membrane permeable to prions? what is the mechanism here?