Cyclic amplification of protein misfolding: application to prion-related disorders and beyond.
Diverse human disorders, including the majority of neurodegenerative diseases, are thought to arise from the misfolding and aggregation of protein. We have recently described a novel technology to amplify cyclically misfolded proteins in vitro. This procedure, named protein misfolding cyclic amplification (PMCA), is conceptually analogous to DNA amplification by PCR and has tremendous implications for research and diagnosis. The PMCA concept has been proved on the amplification of prions implicated in the pathogenesis of transmissible spongiform encephalopathies. In this article we describe the rational behind PMCA and some of the many potential applications of this novel technology.
Soto
Claudio
C
Serono International SA, Geneva, Switzerland. claudio.soto@serono.com
Saborio
Gabriela P
GP
Anderes
Laurence
L
D000818:Animals; D001671:Biochemistry / Q000379:methods*; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001923:Brain Chemistry / Q000502:physiology; D006801:Humans; D018621:PrPC Proteins / Q000378:metabolism* / Q000648:ultrastructure; D018620:PrPSc Proteins / Q000138:chemical synthesis* / Q000378:metabolism* / Q000648:ultrastructure; D017096:Prion Diseases / Q000175:diagnosis* / Q000378:metabolism* / Q000503:physiopathology; D017510:Protein Folding; D020836:Protein Structure, Quaternary / Q000502:physiology*
D018621:PrPC Proteins; D018620:PrPSc Proteins