In the lens aAcrystallin and aB-crystallin subunits combine in a 3:1 ratio to form an,40 mer a-crystallin oligomer. The aB-crystallin gene has a heat shock promoter element and is induced by various stress conditions. aB-Crystallin has been implicated in a number of neurological disorders, such as Alzheimer’s disease and Parkinson’s disease. Both aA-crystallin and aB-crystallin can confer cellular thermo-resistance. Both proteins can act as molecular chaperones, and this chaperoning ability is believed to play a crucial role in maintaining the transparency of the eye lens. As a molecular chaperone, a-crystallin not only prevents the aggregation of unfolded proteins, but it also helps in the refolding of denatured client proteins. Because protein turnover is virtually absent in the lens, many post-translational modifications accumulate in lens proteins during aging. Several studies have shown that these post-translational modifications decrease the chaperone function of a-crystallin, which might be one reason for lens aging and age-related cataract formation. A large number of advanced glycation end products can be found in the aged human lens, which suggests that glycation is a major mechanism for post-translational modification in the aging lens. Glycation is the non-enzymatic reaction that adds carbohydrates, especially glucose, to proteins. First, glucose and other sugars react with the amino groups of proteins to form an unDasatinib stable Schiff’s base that slowly undergoes rearrangement to form a relatively stable Amadori product. Through a series of parallel and sequential reactions, these Amadori products form many AGEs, some of which are fluorescent and colored. The lens contains relatively high levels of methylglyoxal. The reported levels are 1–2 mM. MGO is an a-dicarbonyl compound that reacts with lysine, arginine and histidine residues in proteins to form AGEs, such as hydroimidazolone, argpyrimidine and methylglyoxal lysine dimer. In addition to our own previous findings, others have reported that the aged and cataractous human lenses contain more of these MGO-derived AGEs than the normal lens. Because MGO reacts rapidly with proteins and the lens proteins have long half-lives, it is reasonable to assume that cumulative modification by MGO over many decades of life could be quantitatively significant in the lens proteins. In general, it is believed that AGE formation is a cause for lens protein aging and cataract formation. However, we and others have observed that MGO-AGE formation in aA-crystallin makes it a better chaperone. AGE formation from MGO occurs predominantly in arginine residues of proteins. As a result of these modifications, arginine residues lose their positive charge and become neutral. In a previous study, we demonstrated that the loss of the positive charge was the cause for an increase in the chaperone function of aA-crystallin. In that study, we replaced discrete MGO-modifiable arginine residues with a neutral amino acid, alanine, and showed an improvement in the chaperone function of the mutant proteins. In addition, the chemical conversion of lysine residues to homoarginine residues followed by a reaction with MGO also led to an enhancement in the chaperone function of aA-crystallin.