Question

What are the major PrPsic types in human prion diseases?

Short answer

Answer: The two major PrPsic types in human prion diseases are Type 1 and Type 2. Type 1 PrPsic has an unglycosylated proteinase K-resistant core fragment with a molecular mass of approximately 21 kDa, a higher glycoform ratio for the diglycosylated isoform, and is often associated with sporadic Creutzfeldt-Jakob disease (sCJD), familial CJD, and some cases of iatrogenic CJD. Type 2 PrPsic has an unglycosylated proteinase K-resistant core fragment with a molecular mass of approximately 19 kDa, a lower glycoform ratio for the diglycosylated isoform, and is associated with variant CJD (vCJD), Gerstmann-Sträussler-Scheinker syndrome (GSS), and fatal familial insomnia (FFI). Identifying these PrPsic types is crucial for accurate diagnosis and classification of human prion diseases and can provide valuable insights into their pathogenesis.

Step-by-step solution

Introduction to prion diseases

Prion diseases are a group of rare and fatal neurodegenerative disorders that affect humans and animals. They are caused by the accumulation and abnormal folding of a cellular protein called prion protein (PrPc) into a misfolded, disease-associated isoform known as PrPsic. The altered structure of PrPsic allows it to propagate by inducing the misfolding of normal PrPc proteins, leading to the formation of amyloid aggregates in the brain. These aggregates cause neuronal damage and eventually lead to the clinical symptoms of prion diseases.

The major PrPsic types in human prion diseases

There are two major PrPsic types in human prion diseases, classified as Type 1 and Type 2, based on their biochemical properties, specifically the electrophoretic mobility of the proteinase K-resistant core fragment and the glycoform ratios.

Description of Type 1 PrPsic

Type 1 PrPsic is characterized by an unglycosylated proteinase K-resistant core fragment with a molecular mass of approximately 21 kDa, along with two other bands corresponding to mono- and diglycosylated isoforms. The glycoform ratio for Type 1 PrPsic is typically higher for the diglycosylated isoform, which represents more than 50% of the total PrPsic. Type 1 PrPsic is often associated with sporadic Creutzfeldt-Jakob disease (sCJD), familial CJD, and some cases of iatrogenic CJD.

Description of Type 2 PrPsic

Type 2 PrPsic is characterized by an unglycosylated proteinase K-resistant core fragment with a molecular mass of approximately 19 kDa, which is slightly smaller than that of Type 1. The glycoform ratio for Type 2 PrPsic is typically lower for the diglycosylated isoform, representing less than 50% of the total PrPsic. Type 2 PrPsic is associated with other prion disease subtypes, including variant CJD (vCJD), Gerstmann-Sträussler-Scheinker syndrome (GSS), and fatal familial insomnia (FFI).

Importance of PrPsic typing in human prion diseases

Understanding and identifying the different PrPsic types is crucial for the accurate diagnosis and classification of human prion diseases and their subtypes. The two major PrPsic types, Type 1 and Type 2, are associated with distinct clinical features and disease courses, which can impact both the management and prognosis of affected individuals. Furthermore, the study of PrPsic types can provide valuable insights into the molecular processes involved in the pathogenesis of prion diseases and further our understanding of these complex and devastating neurological disorders.