Discovery of unusual pathogens and how they cause diseases
WHAT IS A PRION ?
Prion is a misfolded protein that causes several neurodegenerative diseases , collectively called transmissible spongiform encephalopathies(TSEs) in animals including humans.This small infectious agent is an aberrant form of a protein called cellular prion protein(PrPC).As stated in Ingram’s book “Fatal Flaws”, before 1982 the tube-nose birds of southern seas were the only prions on earth. But, in 1982, a paper published by American scientist, Stanley Prusiner not only relegated these ornithological prions to back pages but also completely changed the world of CJD,Kuru,Scrapie and a soon-to-be expanded list of diseases.
Fig 1 :Prion protein PrP. Flexible portions of the protein
that are not included in the structures are shown with dots.
Cellular prion protein(PrPc) is a membrane associated protein found in many eukaryotic cells. It is found abundantly on the surface of cells in the central nervous system.It anchors to the neurons via a sugar moiety and functions by transmitting signals between adjacent neurons. A slight change in its three dimensional structure results in a variant insoluble isoform(PrPSc) which hampers the normal process of sensory signal transduction .
BIRTH OF PRIONS
In the 18th century, a strange disease affected Merino sheep.It was termed Scrapie owing to the fact that the affected sheep scraping against the fences, was a clinical diagnostic factor.To understand the nature of the scrapie agent, various experiments were performed including filtration and inactivation by nucleases on scrapie infected tissue.In 1954,Sigurdsson suggested that a slow virus caused this disease due to its long incubation period.
While this was suggested, another neurological disorder was discovered among the Fore tribe in Papua New Guinea called kuru(meaning ‘trembling’ or ‘fear’ in Fore language).Kuru presented similar symptoms to CJD(Creutzfeldt Jakob Disease) and Scrapie.It was not until 1959 that Kuru,CJD and Scrapie were found to be distinct forms of same neuropathy. Meanwhile,some scientists hypothesized that nature of scrapie agent could be a protein.They used ionizing radiation and chemicals(formalin) which usually inactivate pathogens that contained nucleic acid (like viruses and bacteria).In 1982,Stanley Prusiner published a paper in journal Science titled
“Novel Proteinaceous Infectious Particles Cause Scrapie” supporting this idea. Although it was an already established idea , it set off a firestorm among the scientific community , because Prusiner forcefully argued that the infectious agent causing Scrapie could not be anything but a protein and even coined a new name called ‘Prion’ for it.