Transmissible Spongiform Encephalopathies or Prion Diseases - General Introduction

Abstract

Transmissible spongiform encephalopathies (TSEs) form a group of fatal neurodegenerative disorders represented principally by Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome (GSS), and fatal familial insomnia (FFI) in humans, and by scrapie and bovine spongiform encephalopathy (BSE) in animals [1]. Also called prion diseases, TSEs have the unique property of being infectious, sporadic or genetic in origin [2]. They are characterised by a silent asymptomatic period, which may be very long (up to 40 years in humans), in the absence of any specific immune or inflammatory response. During the clinical phase of the disease, specific lesions (spongiosis, astrocytosis) which constitute the veritable signature of these diseases are observed in the central nervous system. The outcome is always fatal for the affected animal or person, whose central nervous system inevitably contains, at the clinical stage of the disease, the transmissible agent which is able to infect another individual of the same species. The nature of this unconventional transmissible agent has not yet been fully elucidated. However, TSEs are almost always accompanied by the accumulation of an abnormal form of a protein in the central nervous system naturally produced by the host, the prion protein, PrP. This abnormal form (called PrP^Sc, for scrapie PrP) sometimes accumulates in brain as amyloid plaques or deposit of which it is the major component. Following the work of Stanley Prusiner [3], a considerable number of experimental findings were accumulated indicating that PrP^Sc could well be the infectious agent itself [4]. PrP^Sc derives from the normal PrP form (PrP^C for cellular PrP) through post-translational modifications which induce a conformational change and confer on PrP^Sc a partial resistance to degradation by proteases, as well as a marked insolubility in the presence of detergents leading to the formation of large aggregates.