Proteomics applications in prion biology and structure

Abstract

Prion diseases are a heterogeneous class of fatal neurodegenerative disorders associated with misfolding of host cellular prion protein (PrP(C)) into a pathological isoform, termed PrP(Sc). Prion diseases affect various mammals, including humans, and effective treatments are not available. Prion diseases are distinguished from other protein misfolding disorders - such as Alzheimer's or Parkinson's disease - in that they are infectious. Prion diseases occur sporadically without any known exposure to infected material, and hereditary cases resulting from rare mutations in the prion protein have also been documented. The mechanistic underpinnings of prion and other neurodegenerative disorders remain poorly understood. Various proteomics techniques have been instrumental in early PrP(Sc) detection, biomarker discovery, elucidation of PrP(Sc) structure and mapping of biochemical pathways affected by pathogenesis. Moving forward, proteomics approaches will likely become more integrated into the clinical and research settings for the rapid diagnosis and characterization of prion pathogenesis.

Keywords: Creutzfeld–Jakob disease; cerebrospinal fluid; mass spectrometry; prion diagnostics; prion disease; prion structure; proteomics; quaking-induced conversion.