Assessment of structure, stability and aggregation of soluble lens proteins and alpha-crystallin upon non-enzymatic glycation: The pathomechanisms underlying cataract development in diabetic patients

•Total soluble lens proteins and α-crystallin were extensively glycated.•The protein glycation was confirmed by different methods.•Glycated crystallins indicate higher conformational stability than non-glycated protein counterparts.•Glycation causes crystallins to resist against stress-induced unfolding and aggregation. Total soluble lens proteins (TSPs) and α-crystallin (α-Cry) were individually subjected to the long-term glycation in the presence of d-glucose. The glycated and non-glycated protein counterparts were incubated under different stress conditions and compared according to their structure, stability and aggregation propensity by various spectroscopic techniques and gel mobility shift analyses. Extensive glycation of the lens proteins was accompanied with structural alteration, reduction in their surface hydrophobicity and increment of their surface tension. Our results suggest that glycation causes lens crystallins to partially resist against structural alteration and aggregation/fibrillation under both thermal and thermochemical systems. The conformational stability of lens crystallins was increased upon glycation, showing the reason behind resistance of glycated proteins against stress-induced structural alteration and aggregation. Due to the resistance of glycated lens crystallins against aggregation, the role of this modification in development of senile cataract can be explained with the associated damaging consequences highlighted in this article.