Applications of the real-time quaking-induced conversion assay in diagnosis, prion strain-typing, drug pre-screening and other amyloidopathies

Expert Rev Mol Diagn. 2017 Oct;17(10):897-904. doi: 10.1080/14737159.2017.1368389. Epub 2017 Sep 8.

Abstract

The development of in vitro protein misfolding amplification assays for the detection and analysis of abnormally folded proteins, such as proteinase K resistant prion protein (PrPres) was a major innovation in the prion field. In prion diseases, these types of assays imitate the pathological conversion of the cellular PrP (PrPC) into a proteinase resistant associated conformer or amyloid, called PrPres. Areas covered: The most prominent protein misfolding amplification assays are the protein misfolding cyclic amplification (PMCA), which is based on sonication and the real-time quaking-induced conversion (RT-QuIC) technique based on shaking. The more recently established RT-QuIC is fully automatic and enables the monitoring of misfolded protein aggregates in real-time by using a fluorescent dye. Expert commentary: RT-QuIC is a very robust and highly reproducible test system which is applicable in diagnosis, prion strain-typing, drug pre-screening and other amyloidopathies.

Keywords: Real-time quaking-induced conversion; aggregation; prion protein; protein misfolding; sporadic Creutzfeldt-Jakob disease.

Publication types

  • Review

MeSH terms

  • Amyloidosis / diagnosis*
  • Amyloidosis / drug therapy
  • Amyloidosis / metabolism*
  • Biological Assay / methods*
  • Biomarkers
  • Body Fluids / metabolism
  • Diagnosis, Differential
  • Drug Discovery / methods
  • Drug Evaluation, Preclinical / methods
  • Humans
  • Prion Diseases / diagnosis*
  • Prion Diseases / drug therapy
  • Prion Diseases / metabolism*
  • Prion Proteins / metabolism
  • Prions / metabolism*
  • Protein Aggregates
  • Protein Aggregation, Pathological

Substances

  • Biomarkers
  • Prion Proteins
  • Prions
  • Protein Aggregates