Ultraviolet irradiation-mediated formation of Aβ42 oligomers and reactive oxygen species in Zn2+-bound Aβ42 aggregates irrespective of the removal of Zn2+

Abstract

The light regulation of the aggregation and disaggregation of metal-bound Aβ peptides remains to be explored. Binding of Zn²⁺ to Aβ peptides is sufficient to trigger the formation of Aβ aggregates. Chelator FC-11 has a high affinity to Zn²⁺ and forms a 1 : 1 complex with Zn²⁺. Although FC-11 can effectively remove the Zn²⁺ ions loaded in the Aβ₄₂ aggregates by chelation, the Zn²⁺ chelation cannot lead to the dissociation of the aggregates. However, controlled UV light exposure was observed to induce the dissociation of Zn²⁺-bound Aβ₄₂ aggregates into sodium dodecyl sulfate (SDS)-resistant soluble oligomers, and this dissociation does not depend on the removal of Zn²⁺ from the aggregates. Moreover, the UV light exposure triggers the production of reactive oxygen species (ROS) including H₂O₂, leading to secondary structural changes in the Aβ₄₂ aggregates. The oxidation and secondary structural changes of the aggregated Aβ₄₂ peptides with Zn²⁺ should contribute to the conversion of the aggregates into soluble oligomers. The formation of ROS and oligomers can result in enhanced cytotoxicity of the aggregates.