Regulation of Prion Protein Expression: A Potential Site for Therapeutic Intervention in the Transmissible Spongiform Encephalopathies

Abstract

The Transmissible Spongiform Encephalopathies (TSEs) are a group of rare neurodegenerative diseases, which can be transmitted between members of the same species and possibly across different species. The link between the emergence of Bovine Spongiform Encephalopathy (BSE) and the new variant form of Creutzfedlt Jakob Disease (vCJD) has been the cause of much public concern. vCJD is the most widely known of the human TSEs but by no means the most common; inherited and sporadic forms are much more prevalent. The agent responsible for these diseases is a conformationally altered form of a normal cell surface glycoprotein, called the prion protein (PrP). The normal isoform must be present for the disease to progress, and disease incubation time decreases with increased PrP expression. There is still no cure for any of these diseases but recent advances in the understanding of how prion protein expression is regulated at the genetic level, and of exogenous factors modulating expression levels, may provide new insights into potential therapeutic targets for disease management by down regulation of cellular PrP levels.