PRION DISEASE
Research Articles
The prion diseases (spongiform encephalopathies; vacuolation of the cerebral gray matter, among other clinical manifestations) are a group of neurodegenerative fatal diseases in humans and other animals. The human diseases can be sporadic, inherited, or acquired, and include Creutzfeld-Jakob disease (CJD), Gerstmann-Straussler-Scheinker disease, fatal familial insomnia, and kuru.
Sporadic CJD accounts for about 85% of the reported cases. The genetic form of CJD is a rare (one or two in a million individuals), progressive, and fatal disease that usually occurs as an autosomal dominant. The mutation is in codon 129 resulting in a change from methionine to valine. Iatrogenic transmission of CJD to patients resulting from inadequately sterilized neurosurgical instrumnets has been reported; also from corneal or dura mater grafting as well as from pituitary growth hormone and gonadotropin obtained from cadavers. The incubation period in variable; from 2 years to 35 years.
Kuru is found among the Fore linguistic group in New Guinea. Infected individuals were usually involved in the preparation of a body (including the brains) for ritualistic cannibalism.
Prion disease is also found in sheep (scrapie), mink, mule deer, Rocky Mountain elk, nyala, gemsbok, cheetah, domestic cats, and cattle [bovine spongiform encephalopathy (BSE), "mad cow disease"]. The disease is associated with the accumulation, in infected brains, of an abnormal form (PrPSc) of a cellular glycoprotein (PrPC). In some transmissible spongiform encephalopathies in humans, there are accumulations of extracellular amyloid plaques; also PrP, in association with Alzheimer's protein, in muslce tissue. The highest titer of the infectious agent, prions, is found in brain tissue.
Prion disease can be experimentally transmitted within and between mammalian species by
inoculation or ingestion of infected tissue; nervous, lymphoid, and muscle tissue. The increase in frequency, in
1995 in England, of sporadic CJD is thought to have been caused by ingestion of
food infected with the prion associated with BSE.
Since the 1940's meat-and-bone meal had been added to cattle feed to "enrich" the animals diet. The "meat" included animal tissue, offal, that had been discarded by the slaughter house. Also, until 1989, homogenates from cattle brains were used in the preparation of hamburgers and sausages.
The mechanism of transmission of acquired prion disease is unique in that the transmitting agent does not appear to have genetic material in the form of RNA or DNA. After the passage of the infectious agent, the prion, from an infected to noninfected individual, the infectious agent enters the lymporeticular system and spreads, via autonomic nerve fibers, to the spinal cord and brain. A structural alteration of the normal cellular protein to the disease causing protein occurs in infected tissue. The disease causing protein itself (PrPSc) seems to acts as a template for this conformational change in the normal cellular protein (PrPC).
PrPC is protease sensitive, soluble in detergent, and primarily alpha helical. PrPSc is protease resistant, insoluble in detergent, and structurally mainly beta-pleated sheet. The normal prion protein, PrPC, is a membrane sialoglycoprotein that may be involved in the utilization of copper.