Oxidative Stress and Neurodegeneration in Prion Diseases

Abstract

Transmissible spongiform encephalopathies (TSEs), also termed prion diseases, are a group of fatal neurodegenerative diseases that affect humans and a number of other animal species. The etiology of these diseases is thought to be associated with the conversion of a normal protein, PrPC, into an infectious, pathogenic form, PrPSc. The PrPSc form shows greater protease resistance than PrPC and accumulates in affected individuals, often in the form of extracellular plaques. The pathogenesis and the molecular basis of neuronal cell death in these diseases are not well understood. Oxidative stress has been proposed to play an important role in the pathogenesis of several neurodegenerative disorders. In the present study, evidence of oxidative stress in scrapie, the archetype disease of the TSEs, is discussed. In addition, the mechanisms whereby oxidative stress could lead to neuronal degeneration are described.