Diseases of protein conformation: what do in vitro experiments tell us about in vivo diseases?

Certain human diseases are associated with proteins that misfold and exhibit decreased solubility under physiological conditions. They result either from mutations that change the amino acid sequence of a protein, or from misfolded wild-type proteins, such as in Parkinson's disease and Alzheimer's disease. One subset – the amyloidoses – cause extracellular deposits that stain with the dye Congo red. Another subset is associated with intracellular deposits with non-Congophilic nuclear or cytoplasmic inclusions. Purified, recombinantly produced versions of some of the proteins that form intracellular aggregates can also display Congophilia, as well as other properties associated with the in vivo amyloidoses when examined under non-physiological conditions in vitro. Some of these purified proteins or protein fragments have never been identified as pathogenic in humans or animals. Despite potentially shared thermodynamic and kinetic processes involving the target molecules, the biology of these two subsets differs significantly.