[The recent progress on the role of alpha-crystallin as a molecular chaperone in cataractogenesis]

The alpha-crystallin is a major structural protein within the lens and consists of two types of subunit, alpha A and alpha B. These subunits propose a model for the quaternary structure of alpha-crystallin. It has been known for many years that its main function is to serve as a structural and refractive elements in lens. Until 1992, Horwitz suggested that alpha-crystallin could act in a chaperone-like manner. Many studies have showed that alpha-crystallin can protect enzymes and other crystallins against both chemically- and thermally-induced inactivation or aggregation, which may play an important role in maintaining transparency of lens. A polypeptide sequence of alpha A-crystallin or extension of alpha B-crystallin in C-terminal-region and hydrophobic N-terminal-region are all essential for chaperone function. A decrease in chaperone activity from nuclear crystallin has been showed in age-dependent fashion. Post-translational modifications occurring to alpha-crystallin with increasing age and during cataract formation may decrease the chaperone activity of alpha-crystallin to different extent, resulting in an increase in other crystallins aggregation and enzymes inactivation. Therefore, these aggregates will increase scattering of light and lead to lens opacification. Development of protective agents for molecular chaperone activity of alpha-crystallin, in conjunction with knowledge of decreasing post-translational modifications, could potentially lead to a new field for the research on pathogenesis and clinical treatment of cataract.