Prion diseases include a group of either sporadic, inherited or infectious disorders characterized by spongiform neurodegeneration and reactive glyosis in several brain regions. Whatever the origin, the neuropathological hallmark of prion diseases is the presence of brain aggregates containing an altered isoform of a cellular protein, named prion protein. Recent findings show the potential toxicity of the normal cellular prion protein, which occurs when its physiological metabolism is altered. In particular, several studies demonstrate that accumulation of the prion protein in the cytosol can be a consequence of an increased amount of misfolded prion proteins, a derangement of the correct protein trafficking or a reduced activity of the ubiquitin-proteasome system. The same effects can be a consequence of a mutation in the gene coding for the prion protein. In all these conditions, one assists to accumulation and self-replication of insoluble prion proteins which leads to a severe disease resembling what observed following typical "prion infections". This article provides an opinion aimed at reconciling the classic Prusiner's theory concerning the "prion concepts" with the present knowledge arising from experimental studies on neurodegenerative disorders, suggesting a few overlapping steps in the pathogenesis of these diseases.

A hypothesis on prion disorders: are infectious, inherited, and sporadic causes so distinct?

FORNAI, FRANCESCO;FERRUCCI, MICHELA;GESI, MARCO;GIORGI FS;PAPARELLI, ANTONIO
2006-01-01

Abstract

Prion diseases include a group of either sporadic, inherited or infectious disorders characterized by spongiform neurodegeneration and reactive glyosis in several brain regions. Whatever the origin, the neuropathological hallmark of prion diseases is the presence of brain aggregates containing an altered isoform of a cellular protein, named prion protein. Recent findings show the potential toxicity of the normal cellular prion protein, which occurs when its physiological metabolism is altered. In particular, several studies demonstrate that accumulation of the prion protein in the cytosol can be a consequence of an increased amount of misfolded prion proteins, a derangement of the correct protein trafficking or a reduced activity of the ubiquitin-proteasome system. The same effects can be a consequence of a mutation in the gene coding for the prion protein. In all these conditions, one assists to accumulation and self-replication of insoluble prion proteins which leads to a severe disease resembling what observed following typical "prion infections". This article provides an opinion aimed at reconciling the classic Prusiner's theory concerning the "prion concepts" with the present knowledge arising from experimental studies on neurodegenerative disorders, suggesting a few overlapping steps in the pathogenesis of these diseases.
2006
Fornai, Francesco; Ferrucci, Michela; Gesi, Marco; BANDETTINI DI POGGIO, A; Giorgi, Fs; Biagioni, F; Paparelli, Antonio
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/199062
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