Cyclic Amplification of Protein Misfolding and Aggregation

  • Paula Saá
  • Joaquín Castilla
  • Claudio Soto
Part of the Methods in Molecular Biology™ book series (MIMB, volume 299)


Diverse human disorders, including most neurodegenerative diseases, are thought to arise from the misfolding and aggregation of an underlying protein. We have recently described a novel technology to amplify cyclically the misfolding and aggregation process in vitro. This procedure, named protein misfolding cyclic amplification (PMCA), conceptually analogous to DNA amplification by PCR, 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 (TSE). In these diseases, there is a tremendous need for early and sensitive biochemical diagnosis to minimize the further spreading of the prion infectious agent through the food chain. In this chapter, we describe the principles behind the PMCA technology, its application, and methodology to detect minute quantities of misfolded prion protein and its potential to be used for amplification of misfolding of other proteins implicated in diverse diseases.

Key Words

Protein conformational disorders prion Creutzfeldt-Jakob disease bovine spongiform encephalopathy Scrapie protein misfolding cyclic amplification (PMCA) Alzheimer's disease amyloid. 


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Copyright information

© Humana Press Inc. 2005

Authors and Affiliations

  • Paula Saá
    • 1
  • Joaquín Castilla
    • 1
  • Claudio Soto
    • 1
  1. 1.Department of NeurologyUniversity of Texas Medical BranchGalveston

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