Prions Alicia Arguelles, Jerry Wang May 4, 2007

What are prions? proteinaceous infectious particle an infectious agent made only of protein, containing no nucleic acids The PRNP gene encodes for the prion protein (PrP) PrP is active in the brain and several other tissues The normal form of the protein is called PrP C, while the infectious form is called Prp Sc

General information Prions are believed to infect and multiply by refolding abnormally into a structure that is able to convert normal protein into an abnormal form. Prions are quite resistant to denaturation by protease, heat, and radiation, almost nothing kills them! In order to be denatured they must be autoclaved at 134 degrees Celsius for 18min. Although, prions have a genetic component, it is also know that they can be transmissible via spongiform encephalopathies.

Different types of prion diseases scrapie (a disease of sheep) chronic wasting disease (in deer and elk) bovine spongiform encephalopathy (BSE or mad cow disease) Gerstmann-Strausler-Scheinker syndrome (GSS) Creutzfeldt-Jacob disease (CJD) Fatal Familial Insomnia (FFI)

Characteristics of prion diseases Also known as TSE (transmissible spongiform encephalopathy) Affects brain or other neural tissue Untreatable and fatal Phenotypic variability Hereditary (10-15%), transmissible, sporadic

Prions and the brain Kuru and vCJD are known to be transmitted to humans who have eaten the meat or brains of infected animals or, in the case of Kuru, infected humans. (Yummy anyone for some brain?)

How Prions Access the Brain.. How can prions, which are merely proteins, make their way through the gut and into the brain, where they cause the scary spongiform encephalitis? We all know that proteins normally are digested down to amino acids in the gut, and transported through the gut epithelium by amino acid transporters. Well if Prions took this route they would not longer be infectious, so… We already know that Prions are extremely resistant to degradation so they are not broken down and digested. Even so, they should not be absorbed across the intestinal wall, right? In fact, they circumvent the normal process of intestinal absorption by passing into the Gut-Associated Lymphoid Tissue (GALT). Related to this, it seems that chronic inflammation predisposes to prion infectivity, e.g. in rheumatoid arthritis, type-I diabetes, or Crohn’s disease.

How Prions Access the Brain Cont.. It is believed that the immune system plays a big role in neuroinvasion. Follicular Dendritic Cells (FDCs) being that they are mobile could function as the bridge between the GI tract and the lymphoid organs, where the prions can replicate. The process by which prions are transported is not fully understood, further research is needed.

Proposed mechanism of prion propagation

Molecular model of PrP c and PrP Sc structures Protein refolds abnormally NormalDiseased

Bovine spongiform encephalopathy (BSE) mad cow disease This is a fatal neurodegenerative disease of cattle An epidemic in Brittish cattle occurred when farmers started to use animal by-product as the main source of feed for their cattle. This lead to an over all higher rate of infection and disease.

Deaths From BSE In the early 1900s a new variant of Creutzfeldt-Jakob disease (vCJD) was discovered and linked to BSE This disease in 2004 had killed 157 people in Europe. 148 cases occurred in the United Kingdom, 6 in France, and 1 in Italy. In the US there have only been 3 vCJD cases reported to date.

Classic Creutzfeldt-Jakob disease vs. Creutzfeldt- Jakob disease (vCJD) CharacteristicClassic CJDVariant CJD Median age of death68 years28 years Median duration of illness4-5 months13-14 months Clinical signs and symptoms Dementia; early neurological signs Prominent psychiatric/behavioral symptoms; painful dysesthesias; delayed neurological signs

Cases of BSE

Summary Prions are toxic because they are not denatured easily and can accumulate in the body. Prions can be ingested via taunted meat and maybe transported by the immune system to the brain where they cause damage. (scientists still are not certain who they get transported) Moral of the story feeding cows animal by-products to save money is not safe for humans.

Sources Center for Disease Control and Prevention, vCJD (Variant Creutzfeldt-Jakob Disease) Chakraborty, C. et al. Prion Disease: A Deadly Disease for Protein Misfolding. Current Pharmaceutical Biotechnology : Gambetti, P. et al. Hereditary Creutzfeldt-Jakob disease and fatal familial insomnia. Clinics in Laboratory Medicine : Mead, Simon. Prion Disease Genetics. European Journal of Human Genetics : Genetics Home Reference. PRNP. National Library of Medicine. November 20, Pearson, George. Oregon State. Prions. Wikipedia Free Encyclopedia, Creutzfeldt-Jakob disease