A Prion is a normal protein that is found on the membranes of cells. The normal Prion protein (PrPC) consist mainly alpha helix rich 30-35kDa glycoprotein with 209 amino acid sequence and one disulfide bond (1). The disease causing form of normal prion protein named after scrapie (PrPSc) occurs when properly folded normal prion protein change its conformation. Although the exact tertiary structure of PrPSc still remains elusive but the previous studies have shown that the secondary structure of infectious protein contains high proportion of beta sheet in place of normal alpha helix. The increased content of beta sheet in PrPSc leads to the formation of aggregates resistant to proteases that assemble into amyloid fibers and accumulate to form plaques in brain cells (2). Prions are extremely small unique pathogens and have no nucleic acid. The PrpSc protein cannot self replicate but causes other normal prion proteins to change the conformation making them infectious. The process by which the infectious prion recruits the normal protein is still unclear. All known prion disease commonly known as transmissible spongiform encephalopathies to date is untreatable and fatal. Some of the common prion disease found in humans includes Creutzfeldt-Jakob disease (CJD), Variant Creutzfeldt-Jakob disease (vCJD), Gerstmann-Straussler-Scheinker Syndrome, Fatal Familial insomnia, and Kuru. Besides human prions disease is also prevalent in animals causing Bovine Spongiform Encephalopathy (BSC) also known as mad cow disease, Chronic Wasting Disease, Scrapie, Transmissible mink encephalophathy, Feline spongiform encephalophathy. The new human prion disease vCJD was first reported in United Kingdom in 1996 and was believed to come from feeding the meat of cattle infected with mad cow disease. Prion disease can be transmitted by ingestion of BSC contaminated food products especially beef and may also be transmitted by using contaminated surgical instruments. It can also be transmitted by blood transfusion or treatment with blood products that were derived from infected donor. The high frequency of disease (Kuru) on those who took part in the ritual eating of the body also suggests that transmission occurs via oral route (3). Once the host is inoculated with the prion disease they first infect tissues that are normally involved in body’s defense mechanism such as spleen and lymph nodes. In vCJD, prions first infect lymphoreticular tissues and then infect brain causing disease symptoms. Unlike other pathogens such as bacteria, fungi or viruses the prion proteins are formed by one of the body’s own proteins and hence cannot be recognized as foreign antigen by host immune system. Lack of nucleic acid along with immune tolerance and size makes prions extremely resistance to protease, heat, radiation making it almost invincible to any known defense mechanism. The incubation period of disease may vary from several years up to 70 years. Evolution of prion disease.
It was believed that Bovine Spongiform Encephalopathy (BSE) in cattle and Creutzfeld-Jakob disease (CJD) in humans originated from prion disease called scrapie found in the sheep. Later it was found that the humans seem unable to get prion diseases from sheep infected with scrapie CJD but by consuming contaminated beef. This strongly suggests that prions in humans did not evolve from the sheep scrapie. The study of fossil of a transmembrane protein in the sequence of known vertebrate PrP suggests that it used to be an integral membrane protein probably expelled to the extracellular space by a mutation (4). Another study suggests that the prion gene is descended from the more ancient ZIP family of metal ion transporters. Members of the ZIP protein family are well known for their ability to transport zinc and other metals across cell membranes (5). This study is consistent with the study of fossils that prion used to be an integral membrane protein as ion transporters belongs to integral...
References: 1. PamKM, Baldwin M, Nguyen J et al. Conversion of alpha helices into beta sheets features in the formation of the scrapie prion protein. Proceedings of the National Acedemics of science of the United State of America 90 (23) : 10962-6. (December 1993).
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