Prions - The killer proteins

The agents of disease, pathogens, are known to be either viral or bacterial in origin. It is only relatively recently that proteins have been implicated in disease. In 1976 Daniel Carleton Gajdusek won the Nobel Prize in physiology or medicine for his work on kuru. Kuru is a neurological disease that is extremely prevalent among the Fore people of Papua, New Guinea. The disease spreads in a way that is suggestive of being infectious, yet the victims show no signs of fever or immune response. Dr. Gajdusek won the Nobel Prize in part for the fact that he explained the method of transmission – cannibalism as practiced during funeral rites among the Fore. But the causative agent remained a mystery; treatment of brain tissue with agents that ordinarily kill viruses or bacteria had no effect. It was not until the early 1980s that Stanley Prusiner of the University of California proposed that proteins were the culprits.

His explanation called the Prison hypothesis won him the Nobel Prize. According to this model, the protein culprit is abnormally shaped or folded and that it serves as a model for other proteins in the nervous system to misfold and aggregate forming plaques. Eventually this process causes nerve cells to stop functioning properly, ultimately leading to death.
His explanation has since been proven to be correct. As a matter of fact, other neurological disorders have been shown to be caused by prions, including scrapie, mad cow disease and Creutzfeldt-Jakob disease. A recent spate of publications suggests that an analogous mechanism may be involved in two dreaded illnesses that appear in old age – Alzheimer’s and Parkinson’s disease. These diseases are not contagious, however, as is the case with true prion diseases. What they do seem to share in common is the fact that they spread through the nervous system in a similar way. To support this hypothesis, a team of investigators injected extracts taken from the brains of Alzheimer’s patients into mice with a susceptibility to the disease. Within a few months, the mice developed wide spread plaques. This work was reported in The Journal of Neuroscience in 2000. This finding suggests that there is a substance in the diseased brain that can “seed” plaque formation.

This is an important finding, for if, in fact, diseases like Alzheimer’s or Parkinson’s develop in this manner, than it may be possible to abort the spread of the affected proteins with specific antibodies or small molecules designed to interact with the suspected agents.