Modulation of alpha-crystallin chaperone activity: a target to prevent or delay cataract?

Cataract, loss of eye lens transparency, is the leading cause of blindness worldwide. alpha-Crystallin, initially known as one of the major structural proteins of the eye lens, is composed of two homologous subunits alphaA- and alphaB-crystallins. It is convincingly established now that alpha-crystallin functions like a chaperone and plays a decisive role in the maintenance of eye lens transparency. The functional ability of alpha-crystallin subunits is to act in cooperation as molecular chaperones to prevent the cellular aggregation and/or inactivation of client proteins under variety of stress conditions. However, chaperone-like activity of alpha-crystallin could be deteriorated or lost during aging or under certain clinical conditions because of various genetic and environmental factors. This review will focus specifically on relevance of alpha-crystallin chaperone function to lens transparency. In particular, we reviewed the studies that demonstrate the modulation of alpha-crystallin chaperone-like activity and discussed the possibility of chaperone-like activity of alpha-crystallin as a potential target to prevent or delay the cataractogenesis.