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The human prion diseases. A review with special emphasis on new variant CJD and comments on surveillance
1Neuropathology Laboratory, Cork University Hospital, Wilton, Cork, Ireland.
Abstract:
The transmissible spongiform encephalopathies or prion diseases represent a new group of diseases with unique clinical and neuropathological features, the transmission of which is both genetic and infectious. The responsible agent is unconventional and appears to be largely composed of a glycoprotein, the prion protein PrP. This is normally present on different cells. In prion diseases, it becomes converted to the pathogenic form PrPres which is resistant to proteinase and accumulates within the brain and this process is accompanied by the development of spongiform change, gliosis and neuronal loss. The human prion diseases include Kuru a progressive cerebellar degeneration with late dementia affecting Fore tribes in New-Guinea, now almost extinct, regarded as being related to cannibalism. Creutzfeldt-Jakob disease is the more frequent human prion disease. Its incidence is approximately one case per million per year. Four variants are now recognized: sporadic, familial, iatrogenic and the new variant. The latter represents a distinct clinico-pathological entity. It is now widely accepted that it is due to the same agent responsible for Bovine Spongiform Encephalopathy in cattle. Gerstmann-Sträussler-Scheinker disease is a very rare inherited disorder due to a number of different mutations in the PRP gene, characterized by abundant deposits of plaque PrPres in the cerebral grey matter. Fatal familial insomnia is another inherited disorder due to a mutation at codon 178 of the PRP gene associated with methionine on codon 129 of the mutant allele. The main neuropathological change is neuronal loss in the thalamus with little or no spongiosis and usually no PrPres deposition. Following the emergence of new variant CJD in 1996, surveillance of all forms of prion diseases has been now been actively introduced in many European nations in order to determine the true incidence and geographic distribution of these rare disorders in humans.
Insights
Transmissible spongiform encephalopathies, or prion diseases, are unique genetic and infectious disorders. The prion protein (PrP) converts to a pathogenic form (PrPres), causing brain damage and neurodegeneration.
Area of Science:
- Neurology
- Pathology
- Infectious Diseases
Background:
- Transmissible spongiform encephalopathies (TSEs), or prion diseases, are a novel class of disorders.
- These diseases exhibit distinct clinical and neuropathological characteristics.
- Transmission occurs through both genetic and infectious routes.
Purpose of the Study:
- To provide an overview of prion diseases.
- To describe the nature of the prion protein (PrP) and its pathogenic form (PrPres).
- To outline the various human prion diseases and their key features.
Main Methods:
- Review of existing literature on prion diseases.
- Description of the molecular mechanisms involving PrP conversion to PrPres.
- Analysis of clinical and neuropathological data from human prion disease cases.
Main Results:
- Prion diseases involve the conversion of normal prion protein (PrP) to a proteinase-resistant form (PrPres).
- This conversion leads to spongiform change, gliosis, and neuronal loss in the brain.
- Human prion diseases include Kuru, Creutzfeldt-Jakob disease (CJD) with its variants, Gerstmann-Sträussler-Scheinker disease, and Fatal Familial Insomnia.
Conclusions:
- Prion diseases are characterized by the accumulation of abnormal prion protein (PrPres).
- Surveillance for human prion diseases has increased globally, particularly following the emergence of new variant CJD.
- Understanding these rare disorders is crucial for public health and research.