Current concepts in human prion protein (Prp) misfolding, Prnp gene polymorphisms and their contribution to Creutzfeldt-Jakob Disease (CJD)

Document Type

Journal Article

Publisher

Jimenez-Godoy, S.A.

Faculty

Faculty of Computing, Health and Science

School

School of Exercise, Biomedical and Health Science

RAS ID

5115

Comments

Michaelsky, K., & Ziman, M. R. (2007). Current concepts in human prion protein (Prp) misfolding, Prnp Gene Polymorphisms and their contribution to Creutzfeldt-Jakob disease (CJD). Histology and Histopathology, 22(10), 1149-1159. Available here

Abstract

Transmissible spongiform encephalopathies are a group of neural degenerative diseases that may be infectious, sporadic, or hereditary and are associated with an abnormally folded prion protein. Unfortunately at the current time it is not at all clear what the normal structure of the prion protein actually is or how it is toxic to cells. Extensive research on prion diseases has led to a dramatic increase in understanding of the pathogenesis of prion disorders, which will hopefully lead to the development of effective treatments. The inability to detect the disease in blood using current technology has made screening difficult. While fortunately there has been a decline in the number of clinical cases of transmissible variant CJD, evidence indicates that very long incubation periods can occur in humans so there may be a long slow, gradual epidemic. In particular, clinical cases in genotypes other than those homozygous for methionine at codon 129 of PRNP have not yet occurred, but such cases might be expected to have longer incubation periods and show differences in pathology to those seen to date. Transgenic animal studies have shown that a large proportion of infected animals develop sub-clinical disease. Moreover, results from a large prevalence study in humans show that several cases test positive but do not develop clinical disease. It is possible therefore that further cases of secondary transmission could occur by iatrogenic spread, which could result in vCJD persisting in the UK at low levels for many years, highlighting the importance of continued vigilance.

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