Molecular Pathology of the Prions

Cellular and Transgenic Models of Familial Prion Diseases

Introduction Prion diseases are fatal neurodegenerative disorders of humans and animals, which result from the conformational conversion of a normal, cell surface glycoprotein (PrPC) into a pathogenic isoform (PrPSc) that is the main component of infectious prions (1,2). Familial prion diseases, which include 10% of the cases of Creutzfeldt-Jakob disease and all cases of Gerstmann-Straussler […]

Central Nervous System Inflammation and Prion Disease Pathogenesis

Introduction The study of inflammation in the prion diseases is relatively new. Indeed, for a number of years the accepted dogma was that the prion diseases lacked an inflammatory response in the brain (1-3). This persists in spite of a number of studies showing that the pathological hallmarks of the prion diseases (PrPSc deposition, astrocytosis, […]

The Electroneuropathology of Prion Disease

Introduction: What Is Electroneuropathology? Neuropathological studies can reveal a great deal about the appearance of cells and structures within the nervous system during the course of a disease, but they cannot determine which neurons were working properly when the samples were taken or in the period before death. Neurons may look normal, but are they […]

Transmissible Spongiform Encephalopathy Neurobiology and Ultrastructure Suggests Extracellular PrPSc Conversion Consistent with Classical Amyloidosis (Pathology of the Prions) Part 1

Introduction The infectious cause of the transmissible spongiform encephalopathies (TSEs), or prion diseases, is not yet clearly defined. Although minorities of researchers cling tenaciously to the virus hypothesis, the prion or protein-only hypothesis is now widely accepted by most scientists working in this field (1). When originally formulated, the protein-only hypothesis proposed that the TSE […]

Transmissible Spongiform Encephalopathy Neurobiology and Ultrastructure Suggests Extracellular PrPSc Conversion Consistent with Classical Amyloidosis (Pathology of the Prions) Part 2

Relationship Between Pathological Change, PrP Accumulation, and Disease Clinical scrapie has been described in sheep and beige mice in the absence of vacuolar changes (8). Similarly, in the Chediak Higashi strain of mink, transmissible mink encephalopathy infection will cause clinical disease, but does not result in vacuolation (45). For these and other reasons, vacuolation does […]

Conformation as Therapeutic Target in the Prionoses and Other Neurodegenerative Conditions

Introduction Neurodegenerative conditions are increasing in prevalence as the average human life expectancy rises. Alzheimer’s disease (AD) is the fourth commonest cause of death in the United States; the recent outbreak of new variant Creutzfeldt-Jakob disease (nvCJD) has raised the specter of a large population being at risk to develop this prionosis. The pathogenesis of […]

Prions of Yeast: From Cytoplasmic Genes to Heritable Amyloidosis Part 1

Introduction It was believed that only proteins could carry out enzymatic reactions, and only nucleic acids could mediate inheritance. In recent years, the work of Cech and Altman and others has shown that nucleic acids can catalyze reactions. Now it has been shown that, in yeast, proteins can mediate inheritance. The infectious protein (prion) concept […]

Prions of Yeast: From Cytoplasmic Genes to Heritable Amyloidosis Part 2

Further Evidence that [URE3] Is a Prion of Ure2p The prion model for [URE3] predicts that the Ure2 protein should be altered in some way in [URE3] strains, compared to wild-type strains. It was shown that, indeed, Ure2p is more protease-resistant in extracts of [URE3] cells than in extracts of (ure-o) cells (Fig. 5; 47). […]

Prions of Yeast: From Cytoplasmic Genes to Heritable Amyloidosis Part 3

[Het-s], A Prion of Podospora Required for a Normal Function Sexual Mating vs Hyphal Anastomosis Most strains of Saccharomyces cerevisiae are diploid, and the starvation conditions that initiate the meiosis-sporulation pathway are commonplace in nature. The haploid mating-competent products of meiosis quickly find a compatible partner, and mating reconstitutes the diploid state. This sexual mating […]