Photoexcited Porphyrins as a Strong Suppressor of β-Amyloid Aggregation and Synaptic Toxicity

• Published in: Angewandte Chemie (International ed.) Vol. 54; no. 39; pp. 11472 - 11476
• Main Authors: Lee, Byung Il, Lee, Seongsoo, Suh, Yoon Seok, Lee, Joon Seok, Kim, Ae-kyeong, Kwon, O-Yu, Yu, Kweon, Park, Chan Beum
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 21.09.2015; WILEY‐VCH Verlag; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Agglomeration; Alzheimer's disease; Amyloid; Amyloid beta-Peptides - chemistry; Amyloid beta-Peptides - toxicity; Amyloidogenesis; Animals; Atomic force microscopy; Cell death; Circular dichroism; Copper; Defects; Dichroism; Drosophila; Drosophila model; Electrophoresis; Fruit flies; Gel electrophoresis; Illumination; Insects; Life span; Light; Locomotion; Neurodegenerative diseases; Neurotoxicity; Peptides; Phenotypes; Photochemical Processes; Photochemicals; Photosensitization; photosensitizers; Porphyrins; Porphyrins - chemistry; Synapses - drug effects; Toxicity; Zinc; β-amyloids; Drosophila model; photosensitizers; Alzheimer’s disease; β-amyloids; porphyrins
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201504310

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 in vitro. 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.