Propagated protein misfolding: New opportunities for therapeutics, new public health risk

. 2015 Aug 6;41(8):196–199. doi: 10.14745/ccdr.v41i08a03

Protein misfolding terminology
Epitope—for proteins, a region or sequence of amino acids which can be recognized by a specific antibody. Exosomes—small (~100nM) membrane-bound vesicles which are secreted by living cells, containing protein and nucleic acids. Prion—infectious aggregate of prion protein, responsible for transmission of CJD¹, scrapie, BSE² and chronic wasting disease. Propagated protein misfolding—prion-like transmission of protein misfolding between cells in an organ such as the brain, mediated by protein aggregates and/or exosomes. Although prion-like, no evidence to date shows natural transmission of disease among or between species. PPM³ seeding—application of prion aggregation theory to propagated protein misfolding aggregates, requiring a specific event in which misfolded monomers aggregate into a productive template (slow kinetics) for recruitment of additional monomers (rapid kinetics). PPM³ strains—application of prion strain behaviour to non-prion propagated protein misfolding, correlating with differences in propagated structure of aggregates of implicated proteins. Post-translational covalent modification—any change in a protein mediated by a chemical bond, such as oxidation and glycosylation.

Protein misfolding terminology

Epitope—for proteins, a region or sequence of amino acids which can be recognized by a specific antibody.
Exosomes—small (~100nM) membrane-bound vesicles which are secreted by living cells, containing protein and nucleic acids.
Prion—infectious aggregate of prion protein, responsible for transmission of CJD¹, scrapie, BSE² and chronic wasting disease.
Propagated protein misfolding—prion-like transmission of protein misfolding between cells in an organ such as the brain, mediated by protein aggregates and/or exosomes. Although prion-like, no evidence to date shows natural transmission of disease among or between species.
PPM³ seeding—application of prion aggregation theory to propagated protein misfolding aggregates, requiring a specific event in which misfolded monomers aggregate into a productive template (slow kinetics) for recruitment of additional monomers (rapid kinetics).
PPM³ strains—application of prion strain behaviour to non-prion propagated protein misfolding, correlating with differences in propagated structure of aggregates of implicated proteins.
Post-translational covalent modification—any change in a protein mediated by a chemical bond, such as oxidation and glycosylation.

¹CJD = Creutzfeldt-Jakob disease ²BSE = bovine spongiform encephalopathy ³PPM = propagated protein misfolding