Photoexcited porphyrins as a strong suppressor of β-amyloid aggregation and synaptic toxicity

Abstract

The abnormal assembly of β-amyloid (Aβ) peptides into neurotoxic, β-sheet-rich amyloid aggregates is a major pathological hallmark of Alzheimer's disease (AD). Light-induced photosensitizing molecules can regulate Aβ amyloidogenesis. Multiple photochemical analyses using circular dichroism, atomic force microscopy, dot blot, and native gel electrophoresis verified that photoactivated meso-tetra(4-sulfonatophenyl)porphyrin (TPPS with M=2H+, Zn2+, Cu2+, Mn2+) successfully inhibits Aβ aggregation invitro. Furthermore, Aβ toxicity was relieved in the photoexcited-TPPS-treated Drosophila AD model. TPPS suppresses neural cell death, synaptic toxicity, and behavioral defects in the Drosophila AD model under blue light illumination. Behavioral phenotypes, including larval locomotion defect and short lifespan caused by Aβ overexpression, were also rescued by blue light-excited TPPS. Photoinduced inhibition of β-amyloid (Aβ) aggregation was achieved with meso-tetra(4-sulfonatophenyl) porphyrin (TPPS, with M=2H+, Zn2+, Cu2+, Mn2+) under blue LED illumination. The light-driven efficacy of TPPS is attributed to the strong binding affinity of TPPS to Aβ and photooxidation of Aβ. Aβ toxicity was relieved in a photoexcited-TPPS-treated Drosophila Alzheimer's disease model.