Distribucion y caracterizacion de la proteina prionica en el encefalo de roedores y en enfermedades prionicas humanas

Resumen

#titulo: distribución y caracterización de la proteina priónica en el encéfalo de roedores y en enfermedades priónicas humanas #RESUMEN: The cellular prion protein (PrPC) is a membrane-bound glycoprotein present in the central nervous system of mammals. Priorts (PrPSc), conformationally-altered isoforms of PrPC, are responsible for transmissible spongiform encephalopathies (tse), a group of neurodegenerative diseases affecting both animals and humans (creutzfeldt-Jakob Disease, CJD; Fatal Familial Insomnia, FFI; Gerstmann-Straussler-Scheinker, GSS; etc.). As the presence of PrPC is necessary for the establishment and further evolution of these pathologies, we have mapped its regional distribution in the rat brain, showing that the study of the chemical nature of the PrPC-containing cells helps explain the selective vulnerability of particular subsets of cells in animal and human TSE. We have al so analyzed two animal models of FFI: i) by injection of neuronal tracers into the thalamus of the rat brain, that supports the existence of a retrograde transport of PrPSc in FFI, and ii) by generation of a line of transgenic mice [Tg(FFi)] that mimics the biochemical reatures of PrP in FFI and helps extrapolation to human subjects. Taken together, the analysis of these animal models successfully explains the most characteristic pathogenic mechanisms of PrPSc in FFI. In human TSE, the study of the PrPSc species associated with the H187R mutation (GSS) outlines the widespread presence of a unique "curly" pattern of PrP immunostain, which appears to be predominantly made up of PrP that is PK-sensitive, and the presence of small amounts of PK-resistant, full-length PrP. The analysis of PrPSc in the new variant CJD (VCJD) significantly expands the number of affected organs with wider implications concerning iatrogenic transmission of VCJD and it also shows the presence of a novel PK-resistant, PrPSc fragment in VCJD that might have important implications concerning the mechanisms of PrPC to PrPSc conversion.