Figure 1

The conventional model for degenerative disease based on mass action and hydrophobic interactions. Monomeric proteins randomly misfold. The chaperone system, including heat shock proteins (HSPs), can reverse the misfolding, and produce normal, functional proteins. However, the misfolded proteins are prone to random oligomerization, and evidence suggests that the resulting oligomers can be toxic. The oligomers aggregate further to form fibrillar aggregates. In each case formation of the misfolded proteins, oligomers and fibrils are considered to lack normal biological functions. These oligomers and fibrillar aggregates can be removed by degradation, which occurs through the actions of the autophagic system and the ubiquitin proteasomal system. Increasing evidence suggests that autophagy is the predominant mechanism of degradation in diseases such as Alzheimer’s disease and Parkinson’s disease [3].