Prion-mediated diseases are an interesting direct application of the
protein folding problem to pathology. It highlights the difference between
kinetic and
thermodynamic stability. The innocuous
alpha helical form folds very quickly and is a
metastable conformation. The disease causing
beta sheet conformation, is energetically slightly more stable, however it is kinetically inaccessible (i.e. it takes a very, very long time to find this conformation randomly). This process is sped up only by
catalysis, where one protein in the disease conformation helps another reach the same shape. Upon doing so, these proteins assemble and form
plaques. These plaques eventually build up in the cells, disrupting normal cell processes, causing disease.
Because prions are proteins and not viruses or bacteria, they are small enough to penetrate the blood brain barrier, which normally keeps disease out of the brain. As a result, these plaques build up in neurons, causing mental illness and eventually death.