Alzheimer's disease (AD) and cataract represent two common protein misfolding diseases closely associated with aging. Growing evidence suggests that these two diseases may be interrelated with each other through cross-sequence interactions between β-amyloid (Aβ) peptide and the short aggregating peptides derived from proteolytic breakdown of α-crystallin. αΑ(66-80) is one of several peptides produced by the proteolytic breakdown of α-crystallin in aged eye lens. Although it is evident that the Aβ(1-40) and αΑ(66-80) coexist in aged eye lenses and both the peptides are known to form macromolecular assemblies, their cross-sequence interaction and the seeding behavior are not known. In this study, the agg... More
Alzheimer's disease (AD) and cataract represent two common protein misfolding diseases closely associated with aging. Growing evidence suggests that these two diseases may be interrelated with each other through cross-sequence interactions between β-amyloid (Aβ) peptide and the short aggregating peptides derived from proteolytic breakdown of α-crystallin. αΑ(66-80) is one of several peptides produced by the proteolytic breakdown of α-crystallin in aged eye lens. Although it is evident that the Aβ(1-40) and αΑ(66-80) coexist in aged eye lenses and both the peptides are known to form macromolecular assemblies, their cross-sequence interaction and the seeding behavior are not known. In this study, the aggregation behavior of αΑ(66-80) has been examined in the presence of Aβ(1-40) on using thioflavin T (ThT) based aggregation kinetics. The presence of monomeric Aβ(1-40) augmented the aggregation kinetics of αΑ(66-80) and reduced the lag time of αΑ(66-80) aggregation. However, the addition of Aβ(1-40) or αΑ(66-80) fibrils (seeds) didn't result in any change in the rate of αΑ(66-80) aggregation. In this in vitro study, we could show that the presence Aβ(1-40) has substantial effect on the aggregation of αΑ(66-80), which suggests a possible interaction between AD and cataract pathologies.
