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Molecular mechanisms of prion pathogenesis


Aguzzi, A; Sigurdson, C; Heikenwaelder, M (2008). Molecular mechanisms of prion pathogenesis. Annual Review of Pathology, 3:11-40.

Abstract

Prion diseases are infectious neurodegenerative diseases occurring in humans and animals with an invariably lethal outcome. One fundamental mechanistic event in prion diseases is the aggregation of aberrantly folded prion protein into large amyloid plaques and fibrous structures associated with neurodegeneration. The cellular prion protein (PrPC) is absolutely required for disease development, and prion knockout mice are not susceptible to prion disease. Prions accumulate not only in the central nervous system but also in lymphoid organs, as shown for new variant and sporadic Creutzfeldt-Jakob patients and for some animals. To date it is largely accepted that prions consist primarily of PrPSc, a misfolded and aggregated beta-sheet-rich isoform of PrPC. However, PrPSc may or may not be completely congruent with the infectious moiety. Here, we discuss the molecular mechanisms leading to neurodegeneration, the role of the immune system in prion pathogenesis, and the existence of prion strains that appear to have different tropisms and biochemical characteristics.

Prion diseases are infectious neurodegenerative diseases occurring in humans and animals with an invariably lethal outcome. One fundamental mechanistic event in prion diseases is the aggregation of aberrantly folded prion protein into large amyloid plaques and fibrous structures associated with neurodegeneration. The cellular prion protein (PrPC) is absolutely required for disease development, and prion knockout mice are not susceptible to prion disease. Prions accumulate not only in the central nervous system but also in lymphoid organs, as shown for new variant and sporadic Creutzfeldt-Jakob patients and for some animals. To date it is largely accepted that prions consist primarily of PrPSc, a misfolded and aggregated beta-sheet-rich isoform of PrPC. However, PrPSc may or may not be completely congruent with the infectious moiety. Here, we discuss the molecular mechanisms leading to neurodegeneration, the role of the immune system in prion pathogenesis, and the existence of prion strains that appear to have different tropisms and biochemical characteristics.

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Additional indexing

Item Type:Journal Article, not refereed, further contribution
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2008
Deposited On:03 Nov 2008 08:38
Last Modified:05 Apr 2016 12:31
Publisher:Annual Reviews
ISSN:1553-4006
Publisher DOI:10.1146/annurev.pathmechdis.3.121806.154326
PubMed ID:18233951
Permanent URL: http://doi.org/10.5167/uzh-4645

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