Protein Misfolding Cyclic Amplification

Prion diseases are caused by a conformational conversion of the cellular prion protein (PrPC) to a pathological conformer (PrPSc). The “prion-only” hypothesis suggests that PrPSc is the infectious agent that propagates the disease acting as a template for the conversion of PrPC. In 2001, we developed a novel technique, called protein misfolding cyclic amplification (PMCA), which mimics in vitro this pathological process in an accelerated way. Thereby, a minimal amount of PrPSc can be amplified several million folds, providing an important tool for the diagnosis and investigation of prion biology, and the molecular mechanism of prion conversion. PMCA also offers a great platform for the study and amplification of the protein misfolding process associated with other neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases. Here we are updating this previously published chapter to incorporate recent advances.