Infectious agent, a hundred times smaller than a virus. Composed of protein, and without any detectable nucleic acid (genetic material), it is strongly linked to a number of fatal degenerative brain diseases in mammals, such as bovine spongiform encephalopathy (BSE) in cattle, scrapie in sheep, and Creutzfeldt–Jakob disease (CJD) and kuru in humans.
The existence of prions was postulated by US neurologist Stanley Prusiner in 1982, when he and his colleagues isolated a single infectious agent for scrapie that consisted only of protein and had no associated nucleic acid (RNA or DNA). His theory has been upheld by subsequent research, which has identified the protein concerned as well as a mechanism for its action.
A US researcher proved that prions are capable of spreading disease, in July 2000, three years after Prusiner was awarded the Nobel Prize for Physiology or Medicine for his prion theory.
Prions have been found to consist of a simple protein called PrP, made up of about 250 amino acids, the gene for which is found normally in mammals, including humans. The protein can exists in two forms: a normal, harmless form (found in white blood cells and on the surface of brain nerve cells and believed to be involved in the trafficking of copper ions) and an abnormal, disease-causing form. The latter is very stable and has been found to be resistant to temperatures as high as 350°C/660°F, ultraviolet radiation, and strong enzymes. It causes infection by setting up a chain reaction that induces the normal protein to fold into the abnormal form. As the prions accumulate in the nervous system, they aggregate to form long filaments that damage the tissues, creating holes in the brain and giving it a characteristic spongy appearance. Because the immune system does not recognize the prions as foreign, no immune reaction develops. In 1992 German researchers showed that mice that lack the PrP gene are not susceptible to scrapie, a finding that strongly supports the theory that normal PrP proteins are necessary for the progression of the disease.
Prion diseases have been found to arise both by transmission from other individuals (through, for example, diet or medical procedures) and by the inheritance of a mutation in the PrP gene. Different mutations give rise to slightly different prions, which accumulate in specific regions of the brain and cause particular symptoms and diseases. About 10% of human prion diseases are hereditary, including CJD and Gerstmann–Sträussler–Scheinker disease (a rare form of dementia). It has been suggested that prions consisting of other, non-PrP proteins might be responsible for other degenerative diseases in humans, including Alzheimer's disease.
The infectivity of prions violates the central dogma of molecular biology inasmuch as it implies the transfer of genetic information (how to form infectious particles) directly from protein to protein, without the usual detour via nucleic acids. This aspect is even clearer in a group of proteins known as yeast prions. While these do not cause any disease, their alternative folded states can lead to different phenotypes, which can be passed on to the next generation without the involvement of nucleic acids.
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