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Understanding Prion Strains: Evidence from Studies of the Disease Forms Affecting Humans.

Authors
  • Rossi, Marcello1, 2
  • Baiardi, Simone3
  • Parchi, Piero4, 5
  • 1 Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna 40138, Italy. [email protected] , (Italy)
  • 2 IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna 40139, Italy. [email protected] , (Italy)
  • 3 Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna 40123, Italy. [email protected] , (Italy)
  • 4 IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna 40139, Italy. [email protected] , (Italy)
  • 5 Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna 40138, Italy. [email protected] , (Italy)
Type
Published Article
Journal
Viruses
Publisher
MDPI AG
Publication Date
Mar 29, 2019
Volume
11
Issue
4
Identifiers
DOI: 10.3390/v11040309
PMID: 30934971
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Prion diseases are a unique group of rare neurodegenerative disorders characterized by tissue deposition of heterogeneous aggregates of abnormally folded protease-resistant prion protein (PrPSc), a broad spectrum of disease phenotypes and a variable efficiency of disease propagation in vivo. The dominant clinicopathological phenotypes of human prion disease include Creutzfeldt⁻Jakob disease, fatal insomnia, variably protease-sensitive prionopathy, and Gerstmann⁻Sträussler⁻Scheinker disease. Prion disease propagation into susceptible hosts led to the isolation and characterization of prion strains, initially operatively defined as "isolates" causing diseases with distinctive characteristics, such as the incubation period, the pattern of PrPSc distribution, and the regional severity of neuropathological changes after injection into syngeneic hosts. More recently, the structural basis of prion strains has been linked to amyloid polymorphs (i.e., variant amyloid protein conformations) and the concept extended to all protein amyloids showing polymorphic structures and some evidence of in vivo or in vitro propagation by seeding. Despite the significant advances, however, the link between amyloid structure and disease is not understood in many instances. Here we reviewed the most significant contributions of human prion disease studies to current knowledge of the molecular basis of phenotypic variability and the prion strain phenomenon and underlined the unsolved issues from the human disease perspective.

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