Random Tidbit: How Spider Silk Forms And Why That Has Anything To Do With Prions And Alzheimer's

According to my notes, the formation of spider silk involves a conversion from the globular, alpha helical conformation of the silk protein to an insoluble, beta pleated sheet conformation of the silk protein. This is somehow accomplished by the spider "spinning" the silk protein.

You might wonder how this is highly relevant to veterinary medicine. It was cited in my notes on transmissible spongiform encephalopathies as another example of proteins changing conformation. The more clinically relevant example is the conversion of the prion protein from an alpha helical conformation to a beta sheet conformation that induces other prion proteins to change conformation, which leads to the formation of incredibly stable fibrils that accumulate in plaques visible on stained sections of diseased brain.

The formation of amyloid (insoluble plaques of the beta sheet conformation of a protein) is also a hallmark of other neurodegenerative diseases, such as Alzheimer's disease and Huntington's disease. Although not my area of expertise, I worked in a lab that studied Alzheimer's disease and so am familiar with both it and prions circa 2000 or so. (In fact, geek that I am, I used to have a depiction of the prion protein from a biochemistry article hanging in my bedroom in college-- at least I put up artwork then. Now my walls are bare).

I'm surprised to learn that there haven't been any significant breakthroughs in either field since my college days. The closest we've come to a treatment for prion diseases is curing yeast of a prion-like protein, the extrachromosomal element PSI+. The experiment identified a chaperone involved in thermotolerance in yeast that was able to cause the PSI+ protein to convert back to its normal conformation. It's a long way from yeast to mammals and this was all work done before 2000.

Among many unanswered questions in the field, the one I most expected to be answered by now was what is the role of the normally folded prion protein in the body? Genetic knockouts didn't show any abnormalities so this remains a mystery. But prions are conserved in all vertebrates so they must have played an important evolutionary role at some point in time.

On a simpler note, one thing that I've never understood-- prion stands for proteinaceous infectious particle. How does one get prion out of three words that have the acronym PIP?

Perhaps tomorrow I will write what little I know about Alzheimer's disease.

Oh yeah, in case you are wondering what falls under the category of transmissible spongiform encephalopathies:

Creutzfeldt-Jacob disease (familial and the sporadically occuring variant), which is the same as Kuru
Bovine Spongiform Encephalopathy aka "Mad Cow Disease"
Chronic Wasting Disease (found in cervids-- deer)
Transmissible Mink Encephalopathy
Feline Spongiform Encephalopathy
Gerstmann-Straussler-Schneinker Syndrome
Scrapie
and my all-time personal favorite--
Fatal Familial Insomnia