Human prion diseases: novel diagnostic principles

Abstract

Prion diseases include a wide range of diseases affecting both humans and animals. One commom feature of this diverse group of diseases is the deposition of PrPSc, the abnormally folded form of the host encoded prion protein. The proposed replicative cycle of prions is relatively simple. It encompasses misfolding of a single protein, the cellular prion protein PrPC, into a disease-associated form termed PrPSc. This is followed by PrPSc aggregation, and possibly fragmentation of aggregates which may augment the number of replicative units. While there is no formal proof of the correctness of the above model, a wealth of evidence indicates that pathogen-encoded informational nucleic acids are dispensable for prion replication. The detection of prpSc in various tissue compartments including the central nervous system, the lymphoreticular system and skeletal muscle is the principle of the majority of diagnostic test aimed to verify the clinical suspicion of a prion disease. This article discusses current concepts surrounding the basic biology of prions and the diagnosis of prion diseases.