CSIR NET LIFE SCIENCE COACHING IN DELHI

Dr. Charu S

PRIONS

The laughing sickness and mad cow; infectious proteins at work.

During the 1950s-60s, an epidemic of a rare and fatal brain disorder was observed among the Fore people in the highlands of New Guinea  ( Australia).

The disease was called Kuru, which means the “shaking or shivering disease”.  This disease mainly affects the cerebellum; a part of the brain, which is responsible for coordination.  The initial symptoms were an unsteady gait, sporadic muscle jerks, slurred speech and inappropriate laughter. The result is fatal.

Anthropological studies established that the disease was transmitted by the practice of mortuary cannibalism i.e where the remains of the dead were prepared and consumed by relatives of the deceased. Those that died of kuru were highly regarded as sources of food, because they had layers of fate which resembled pork. Disease could spread to women though open cuts or wounds while handling the remains. Morsels of soft tissue, such as the brain, were fed to young children and elderly relatives. Therefore, it was women, children and the elderly who most often became infected.

The Australian Government actively discouraged the practice of cannibalism. This has led to the disappearance of the disease today.

Kuru belongs to a class of infectious diseases called transmissible spongiform encephalopathies (TSEs), so called because they frequently cause the brain to become spongy and riddled with holes. These are extremely rare and fatal neurodegenerative conditions.  

Stanley Prusiner proposed the prion hypothesis in 1982. He and coworkers purified the infectious particles, called prions which were proposed to be responsible for the occurrence of TSEs, thus establishing  that prions are infectious protein particles. TSEs are believed to be transmitted by an abnormally folded form of a cellular protein named PrP.

PrP^C is normal cell membrane protein which in vivo has been found to have a role in cell-cell adhesion and intracellular signalling. It may therefore be involved in cellular communication in the brain.  The infectious isoform of PrP, is known as PrP^SC; after scrapie.  If a prion enters a healthy organism, it may propagate itself by transmitting a misfolded protein state. PrP^SC acts as a template to guide the misfolding of the normal PrP^C proteins into the infectious isoform. This misfolding can be further propagated as a chain reaction.  

Pr^SC proteins form extracellular insoluble aggregates of highly structured amyloid fibers, which accumulate to form plaques, within the central nervous system. This disrupt the normal tissue structure, creating "holes" or a spongy appearance of the brain tissue.  

The neurodegenerative diseases caused by prions can be infectious, or inherited.  The inherited forms are caused by mutations of the human PrP gene named PRNP.  The infectious forms are transmitted through contact with or consumption of previously infected tissues.

Other TSEs include Creutzfeldt-Jakob disease (CJD), variant Creutzfeldt-Jakob disease(vCJD),  fatal familial insomnia in humans, bovine spongiform encephalopathy (BSE) in cattle (also known as mad cow disease), scrapie in sheep and goats, and chronic wasting disease in deer and elk

In 1986, BSE or mad cow disease, first appeared in the UK. The first human victims of vCJD were reported in the late 1990s. It was realized, that the practise of feeding offal (organs and entrails of butchered animals) was resulting in the spread of disease in livestock.  Consumption of infected beef resulted in transmission to humans. A worldwide ban on British beef was imposed by the European Commission, and more than 20, 000 cattle was culled by the British government in order to contain the disease