Prion Protein Strain Diversity and Disease Pathology

*Saima Zafar, Neelam Younas, Mohsin Shafiq and Inga Zerr*

### **Abstract**

The infectious agents, prions, are composed mainly of conformational isomers of the cellular prion protein (PrPc) in its abnormal accumulated scrapie forms (PrPSc). The distinct prion isolates or strains have been associated with different PrPSc prion protein conformations and patterns of glycosylation and are associated with disease progression and severity. In humans, sporadic Creutzfeldt-Jakob disease (sCJD) is the most common form and has been divided into six subtypes, based on PrPSc electrophoretic mobility and allelic variation at codon 129, among which sCJD MM1 and sCJD VV2 are the two most commonly occurring subtypes with known clinical manifestations. The strainspecific response of PrPSc suggests both the molecular classification and the pathogenesis of prion diseases along with posttranslational modification of PrP in humans and animals.

**Keywords:** prion strain, CJD, conformation, dynamics, aggregation

#### **1. Introduction**

For the last two decades, scientists have been working on the prion-related diseases, though major features of this transmissible neurodegenerative disease are still not clear. Among some ambiguities, the prion strain phenomenon and the zoonotic potential are the most discussed and enigmatic questions.

Prion diseases are fatal neurodegenerative disorder linked with misfolding of the host-derived protein, named prion protein. The prevalence of the disease in human population is very low (i.e., ~1–2 cases per million) and affect typically aged people. Among this 15% showed genetic concomitant, i.e., point mutation in *PRNP* gene.

Prion diseases are also well-known risk factor for ruminants, including sheep and goats with scrapie, cattle with bovine spongiform encephalopathy, and recently cervids with chronic wasting diseases (CWD). The prion agent was not able to cross the species barriers between humans and ruminant to a high extent, until the new application livestock carcasses recycling into the ruminant alimentary chain. This new implementation resulted in partial inactivation of the BSE prions and cemented the approach with zoonotic potential and spread in humans. This outbreak was famous as the mad cow disease in cattle and the variant CJD (vCJD) in humans. The prion strain diversity, potential to adapt from one host to another, is a mysterious character-impelled scientific community to uncover the concealed story behind.
