Prions

Original Image found at http://www.mpibpc.mpg.de/groups/grubmueller/start/people/mstumpe1/index.html
The diseases caused by prions are frustrating in terms of trying to heal a person infected, but fascinating and intriguing when viewed strictly through scientific eyes.  Prions lack all genetic material and are unlike any other known pathogen.  Because prions alter the genetic material in normal proteins, and are able to do so quickly, there is no way to stop them.  Once the prions begin to change the conformation of a few proteins, the change for surrounding proteins is not far behind.  The gene that codes for prions can mutate and be passed on to the next generation.  Specifically, prions tend to cause a mutation in chromosome 20, especially in humans and other mammals.  Incredibly, the variability of the codon in the the amino acid sequence that is altered hardly varies among similar organisms.  For example, in the case of CJD codon 129 is where the mutation occurs, every time.  For Scrapie and BSE the codon changes tend to occur at codons 136, 154, and 171.

Diagram shows brain areas affected by prion diseases. Courtesy of http://whyfiles.org/193prion/3.html. 

Pathogenesis of Prion Diseases

*CJD is the specific example here, but the pathogenesis is very similar among all TSEs.

*This pathogenesis process was taken from Northeastern Ohio's Universities College of Medicine Neuropathology.

  • Misfolding of the normal prion protein (PrPC) converts it to an insoluble, protease resistant isoform (PrPSc), which precipitates as amyloid.
    loss by some unknown mechanism.
     
  • In familial CJD, mutations of the Prion protein gene cause prions to misfold.
    It is not clear what causes sporadic CJD. Polymorphisms of the prion protein gene at codon 129 increase susceptibility and influence the phenotype of sporadic CJD.
     
  • In iatrogenic and variant CJD, PrPSc introduced into the brain induce PrPC to misfold. Endogenous PrPSc produced in familial and sporadic CJD also has the same effect.

Among humans the different TSEs include Creutzfeldt-Jakob disease, Gerstmann-Straussler syndrome, Fatal familial insomnia, and Kuru.  In other mammals there are well known prion diseases such as Mad Cow Disease, Scrapie, Chronic wasting disease, and others.  However, as research among different organisms continues, it is becoming clear that many of them suffer from prion presence and TSEs.

Swollen eye and pus at pedicle due to CAS. Courtesy of Wisconsin DNR. Abscess extending from antler pedicle through skull into brain. Courtesy of Wisconsin DNR.

There is no known treatment for TSEs, prevention is the key!  Take a look at this short slideshow which shows an animation indicating how the proteins are changed in shape and function.