94 - Prion Diseases

Abstract

Prion (pronounced pree-ahn) diseases (PrDs) are a group of uniformly fatal neurodegenerative diseases caused by the transformation of an endogenous protein, PrP (prion-related protein), into an abnormal conformation (misfolded protein) called the prion. The term "prion" is derived from the term "proteinaceous infectious particle" and was named by Stanley Prusiner, who discovered prions. For many years, prion diseases were mistakenly thought to be due to “slow viruses,” in part owing to the transmissibility of the diseases and the long incubation period between exposure and symptom onset. Research by Prusiner and others, however, determined that the infectious agent did not contain nucleic acid, a component of viruses. Furthermore, treating prion-contaminated material with methods that inactivated viruses and other microorganisms did not prevent these diseases from being experimentally transmitted; yet methods that denatured or destroyed proteins prevented transmission, strongly supporting the theory that the causative agent was a protein. The identification of the gene-encoding human PrP, PRNP, and mutations of this gene in patients with familial prion disease further helped support the prion hypothesis. In 1997, Stanley B. Prusiner received the Nobel Prize in Physiology or Medicine for his work on identifying the prion. Through animal models, identification of prion gene mutations causing prion disease in humans, and in vitro production of prions with transmissibility, it essentially has been proven that the prion protein is necessary and sufficient to cause prion disease. Although PrDs occur in animals and humans, this chapter will focuses on human PrDs, only discussing animal prion diseases relevant to human disease.