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.
Crabbe
M J
MJ
Division of Cell and Molecular Biology, School of Animal and Microbial Sciences, The University of Reading, Berkshire, UK.
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D002386:Cataract / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D003459:Crystallins / Q000737:chemistry* / Q000378:metabolism; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000378:metabolism; D006801:Humans; D015416:Maillard Reaction; D011487:Protein Conformation; D017510:Protein Folding; D011499:Protein Processing, Post-Translational
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003459:Crystallins