Cataract as a conformational disease--the Maillard reaction, alpha-crystallin and chemotherapy

Cataract, the major cause of blindness world-wide, is associated with conformational changes and unfolding of proteins in the lens, which can arise directly as a result of post-translational modifications, induced by the Maillard reaction. In the lens, the stress protein alpha-crystallin, which is related to small heat-shock proteins and forms GroEL-like functional aggregates, can act as a chaperone-like protein to maintain transparency, sequestering unfolded protein, and inhibiting subsequent aggregation and insolubilisation. There are a number of criteria which enable the classification of cataract as a conformational disease, including not only the protein conformational change itself, resulting in aggregation and tissue deposition, but also the mechanisms for preventing such unfolding and aggregation. Post-translational modification of alphabeta-crystallin results in loss of chaperone-like activity, and aspirin, ibuprofen and paracetamol can inhibit in vitro cross-linking events responsible for the loss of this activity. Of the many avenues available to block protein aggregation, common analgesics--and vitamin C--may provide a cost-effective route to explore further in the treatment of a range of conformational diseases.