Metal-catalyzed proteolysis, conformational antigenicity, photosensitized oxidation, and electrical dysfunction...

It is widely accepted that protein aggregates tend to be pathologic, although little is known about why they are pathologic. Here, we summarize published findings about protein aggregates which have implications for pathology, but which have not yet been covered in any review or hypothesis on the subject, to the best of our knowledge. These findings suggest that protein aggregates can: (i) act as proteases, using exposed surface serines, (ii) function as immunogens, using novel conformational epitopes, (iii) behave as photosensitization-aids, using a novel peptide-based fluorescence, and (iv) act as electrical conductors, using electrons tunneling through hydrogen-bonded networks of peptide bonds. The potential pathological consequences of each finding are speculated upon.