Molecular pathology of human prion disease
Open Access
- 8 August 2010
- journal article
- research article
- Published by Springer Science and Business Media LLC in Acta Neuropathologica
- Vol. 121 (1), 69-77
- https://doi.org/10.1007/s00401-010-0735-5
Abstract
Human prion diseases are associated with a range of clinical presentations and are classified by both clinicopathological syndrome and aetiology with sub-classification according to molecular criteria. Considerable experimental evidence suggests that phenotypic diversity in human prion disease relates in significant part to the existence of distinct human prion strains encoded by abnormal PrP isoforms with differing physicochemical properties. To date, however, the conformational repertoire of pathological isoforms of wild-type human PrP and the various forms of mutant human PrP has not been fully defined. Efforts to produce a unified international classification of human prion disease are still ongoing. The ability of genetic background to influence prion strain selection together with knowledge of numerous other factors that may influence clinical and neuropathological presentation strongly emphasises the requirement to identify distinct human prion strains in appropriate transgenic models, where host genetic variability and other modifiers of phenotype are removed. Defining how many human prion strains exist allied with transgenic modelling of potentially zoonotic prion strains will inform on how many human infections may have an animal origin. Understanding these relationships will have direct translation to protecting public health.This publication has 125 references indexed in Scilit:
- Genetic risk factors for variant Creutzfeldt–Jakob disease: a genome-wide association studyThe Lancet Neurology, 2009
- Detection and characterization of proteinase K-sensitive disease-related prion protein with thermolysinBiochemical Journal, 2008
- A novel human disease with abnormal prion protein sensitive to proteaseAnnals of Neurology, 2008
- Kuru prions and sporadic Creutzfeldt–Jakob disease prions have equivalent transmission properties in transgenic and wild-type miceProceedings of the National Academy of Sciences of the United States of America, 2008
- Prions of fungi: inherited structures and biological rolesNature Reviews Microbiology, 2007
- Proteinase K-sensitive disease-associated ovine prion protein revealed by conformation-dependent immunoassayBiochemical Journal, 2006
- Dissociation of pathological and molecular phenotype of variant Creutzfeldt–Jakob disease in transgenic human prion protein 129 heterozygous miceProceedings of the National Academy of Sciences of the United States of America, 2006
- The most infectious prion protein particlesNature, 2005
- Prions as adaptive conduits of memory and inheritanceNature Reviews Genetics, 2005
- Prevalence of lymphoreticular prion protein accumulation in UK tissue samplesThe Journal of Pathology, 2004