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 ca n arise directly as a result of post-translational modifications, indu ced by the Maillard reaction. In the lens, the stress protein alpha-cr ystallin, which is related to small heat-shock proteins and forms GroE L-like functional aggregates, can act as a chaperone-like protein to m aintain transparency, sequestering unfolded protein, and inhibiting su bsequent aggrgation and insolubilisation. There are a number of criter ia which enable the classification of cataract as a conformational dis ease, including not only the protein conformational change itself resu lting in aggregation and tissue deposition, but also the mechanisms fo r preventing such unfolding and aggregation. Post-translational modifi cation of alpha beta-crystallin results in loss of chaperone-like acti vity, and aspirin, ibuprofen and paracetamol can inhibit in vitro cros s-linking events responsible for the loss of this activity. Of the man y 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.