TY - JOUR
T1 - Recent advances in the histo-molecular pathology of human prion disease
AU - Baiardi, Simone
AU - Rossi, Marcello
AU - Capellari, Sabina
AU - Parchi, Piero
N1 - Ricercatori distaccati presso IRCCS a seguito Convenzione esclusiva con Università di Bologna (Capellari Sabina,Parchi Piero).
PY - 2019/3/1
Y1 - 2019/3/1
N2 - Prion diseases are progressive neurodegenerative disorders affecting humans and other mammalian species. The term prion, originally put forward to propose the concept that a protein could be infectious, refers to PrP Sc , a misfolded isoform of the cellular prion protein (PrP C ) that represents the pathogenetic hallmark of these disorders. The discovery that other proteins characterized by misfolding and seeded aggregation can spread from cell to cell, similarly to PrP Sc , has increased interest in prion diseases. Among neurodegenerative disorders, however, prion diseases distinguish themselves for the broader phenotypic spectrum, the fastest disease progression and the existence of infectious forms that can be transmitted through the exposure to diseased tissues via ingestion, injection or transplantation. The main clinicopathological phenotypes of human prion disease include Creutzfeldt–Jakob disease, by far the most common, fatal insomnia, variably protease-sensitive prionopathy, and Gerstmann–Sträussler–Scheinker disease. However, clinicopathological manifestations extend even beyond those predicted by this classification. Because of their transmissibility, the phenotypic diversity of prion diseases can also be propagated into syngenic hosts as prion strains with distinct characteristics, such as incubation period, pattern of PrP Sc distribution and regional severity of histopathological changes in the brain. Increasing evidence indicates that different PrP Sc conformers, forming distinct ordered aggregates, encipher the phenotypic variants related to prion strains. In this review, we summarize the most recent advances concerning the histo-molecular pathology of human prion disease focusing on the phenotypic spectrum of the disease including co-pathologies, the characterization of prion strains by experimental transmission and their correlation with the physicochemical properties of PrP Sc aggregates.
AB - Prion diseases are progressive neurodegenerative disorders affecting humans and other mammalian species. The term prion, originally put forward to propose the concept that a protein could be infectious, refers to PrP Sc , a misfolded isoform of the cellular prion protein (PrP C ) that represents the pathogenetic hallmark of these disorders. The discovery that other proteins characterized by misfolding and seeded aggregation can spread from cell to cell, similarly to PrP Sc , has increased interest in prion diseases. Among neurodegenerative disorders, however, prion diseases distinguish themselves for the broader phenotypic spectrum, the fastest disease progression and the existence of infectious forms that can be transmitted through the exposure to diseased tissues via ingestion, injection or transplantation. The main clinicopathological phenotypes of human prion disease include Creutzfeldt–Jakob disease, by far the most common, fatal insomnia, variably protease-sensitive prionopathy, and Gerstmann–Sträussler–Scheinker disease. However, clinicopathological manifestations extend even beyond those predicted by this classification. Because of their transmissibility, the phenotypic diversity of prion diseases can also be propagated into syngenic hosts as prion strains with distinct characteristics, such as incubation period, pattern of PrP Sc distribution and regional severity of histopathological changes in the brain. Increasing evidence indicates that different PrP Sc conformers, forming distinct ordered aggregates, encipher the phenotypic variants related to prion strains. In this review, we summarize the most recent advances concerning the histo-molecular pathology of human prion disease focusing on the phenotypic spectrum of the disease including co-pathologies, the characterization of prion strains by experimental transmission and their correlation with the physicochemical properties of PrP Sc aggregates.
KW - amyloidosis
KW - Creutzfeldt–Jakob disease
KW - fatal insomnia
KW - Gerstmann–Sträussler–Scheinker disease
KW - human prions
KW - neurodegenerative dementia
KW - prion strains
UR - http://www.scopus.com/inward/record.url?scp=85060546551&partnerID=8YFLogxK
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U2 - 10.1111/bpa.12695
DO - 10.1111/bpa.12695
M3 - Review article
C2 - 30588685
AN - SCOPUS:85060546551
VL - 29
SP - 278
EP - 300
JO - Brain Pathology
JF - Brain Pathology
SN - 1015-6305
IS - 2
ER -