Prion protein amyloidosis

Research output: Contribution to journalReview article

157 Scopus citations

Abstract

The prion protein (PrP) plays an essential role in the pathogenesis of a group of sporadic, genetically determined and infectious fatal degenerative diseases, referred to as 'prion diseases', affecting the central nervous system of humans and other mammals. The cellular PrP is encoded by a single copy gene, highly conserved across mammalian species. In prion diseases, PrP undergoes conformational changes involving a shift from α-helix to β-sheet structure. This conversion is important for PrP amyloidogenesis, which occurs to the highest degree in the genetically determined Gerstmann-Straussler-Scheinker disease (GSS) and prion protein cerebral amyloid angiopathy (PrP-CAA), while it is less frequently seen in other prion diseases. GSS and PrP-CAA are associated with point mutations of the prion protein gene (PRNP); these conditions show a broad spectrum of clinical presentation, the main signs being ataxia, spastic paraparesis, extrapyramidal signs and dementia. In GSS, parenchymal amyloid may be associated with spongiform changes or neurofibrillary lesions; in PrP-CAA, vascular amyloid is associated with neurofibrillary lesions. A major component of the amyloid fibrils in the two diseases is a 7 kDa peptide, spanning residues 81-150 of PrP.

Original languageEnglish (US)
Pages (from-to)127-145
Number of pages19
JournalBrain Pathology
Volume6
Issue number2
DOIs
StatePublished - Apr 1996

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ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)
  • Clinical Neurology

Cite this

Ghetti, B., Piccardo, P., Frangione, B., Bugiani, O., Giaccone, G., Young, K., Prelli, F., Farlow, M. R., Dlouhy, S. R., & Tagliavini, F. (1996). Prion protein amyloidosis. Brain Pathology, 6(2), 127-145. https://doi.org/10.1111/j.1750-3639.1996.tb00796.x