During the last 5–10 years, it has been realized that a large number of diseases
with very different pathologies at the cellular level can be discussed
within a common framework of defective protein folding. Although the
molecular mechanisms by which the pathologies develop are quite different,
they can all be viewed as “conformational diseases.” The original concept of
conformational disease was developed in relation to disorders whose hallmark
was intra- or extracellular accumulation of protein aggregates, such as seen in
α-1-antitrypsin deficiency with liver pathology, Alzheimer’s, Parkinson’s, and
Huntington’s diseases (AD/PD/HD) (1–3). The basis for the pathology in these
diseases is a cellular inability to degrade misfolded and damaged proteins and
formation of cytotoxic intra- or extracellular oligomers and polymers/aggregates.
The pathology in these diseases is predominantly determined by the cell
damage associated with the aggregation process, thus exhibiting what can be
considered a “gain-of-function” pathology