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Title: Molecular clues to pathogenesis in prion diseases
Issue Date: 1997
Publisher: Murcia : F. Hernández
ISSN: 0213-3911
Related subjects: CDU::6 - Ciencias aplicadas::61 - Medicina
Keywords: Prion diseases
Prion protein
Abstract: The infectious agent of the transmissible spongiform encephalopathies (TSE) resembles a virus in that it propagates in vivo and has distinct strains. However, compelling evidence strongly suggests that a posttranslational structural alteration in a glycoprotein P ~ PC(t he normal, cellular isoform of the so-called prion protein) is responsible for pathogenesis of these diseases. According to this hypothesis - now close to being generally accepted -, iatrogen, sporadic and familia1 forms of TSE would have the same molecular mechanism: the conversion of PrPC into a proteaseresistant isoform prPSc kinetically behaves as an autocatalytic process which, combined with the high turnover rate of the normal isoform, may endow the system with bistability properties and subsequent threshold behavior between normal and pathogenic steady-states. Normal prion protein seems to be necessary for long-term survival of Purkinje neurons, regulation of circadian rhythms and, more controversially, for normal synaptic function. At least part of the pathology might be due to the unavailability of normal isoform rather than to the accumulation of PrPSc. NMR structure of the normal mouse prion protein reveals a short, unexpected B-sheet which might be a nucleation site for the conformational transition between P ~ PCa nd P~PSCP.r ion diseases may challenge the edged distinction that we use to make between informational (DNA) and functional (proteins) macromolecules. Pathogenic mechanism of prions might also be involved in other proteins to achieve and pass on their conformation. Hence, structural inheritance at the molecular leve1 might be the missing link for the understanding of the structural inheritance processes featured at the cellular level. Moreover, evolutionary paradigm postulating a primitive RNA world is weakened by the mechanism of prion diseases.
Primary author: Laurent, M.
Johannin, G.
Published in: Histology and histopathology
Document type: info:eu-repo/semantics/article
Number of pages / Extensions: 12
Rights: info:eu-repo/semantics/openAccess
Appears in Collections:Vol.12, nº 2 (1997)

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