Shedding Light on Alzheimer’s β-Amyloidosis: Photosensitized Methylene Blue Inhibits Self-Assembly of β-Amyloid Peptides and Disintegrates Their Aggregates

• Published in: Scientific reports 2017-08, Vol.7 (1), p.7523-10, Article 7523
• Main Authors: Lee, Byung Il, Suh, Yoon Seok, Chung, You Jung, Yu, Kweon, Park, Chan Beum
• Format: Article
• Language: English
• Subjects: 13/51; 631/154; 639/638/439; 64/24; 692/617/375/365/1283; 82; 82/29; 96/34; Aggregates; Alzheimer Disease - drug therapy; Alzheimer Disease - metabolism; Alzheimer Disease - physiopathology; Alzheimer's disease; Amyloid beta-Peptides - antagonists & inhibitors; Amyloid beta-Peptides - chemistry; Amyloid beta-Peptides - metabolism; Amyloidosis; Amyloidosis - drug therapy; Amyloidosis - metabolism; Amyloidosis - pathology; Amyloidosis - physiopathology; Animals; Brain - drug effects; Brain - metabolism; Brain - pathology; Brain research; Clinical trials; Cytotoxicity; Disease Models, Animal; Drosophila melanogaster; Drug development; Humanities and Social Sciences; Humans; Insects; Light; Locomotion; Locomotion - drug effects; Locomotion - physiology; Methylene blue; Methylene Blue - chemistry; Methylene Blue - pharmacology; Methylene Blue - radiation effects; multidisciplinary; Neurodegenerative diseases; Neuromuscular Junction - drug effects; Neuromuscular Junction - metabolism; Neuromuscular Junction - pathology; Neuromuscular junctions; Neuroprotective Agents - chemistry; Neuroprotective Agents - pharmacology; Nootropic Agents - chemistry; Nootropic Agents - pharmacology; Oxidation; Oxidation-Reduction; Peptide Fragments - antagonists & inhibitors; Peptide Fragments - chemistry; Peptide Fragments - metabolism; Peptides; Photochemicals; Photochemotherapy - methods; Photodynamic therapy; Photosensitizing Agents - chemistry; Photosensitizing Agents - pharmacology; Protein Aggregates - drug effects; Science; Science (multidisciplinary); Self-assembly; Singlet Oxygen - chemistry; Singlet Oxygen - pharmacology; Toxicity; β-Amyloid
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-07581-2

Abnormal aggregation of β-amyloid (Aβ) peptides is a major hallmark of Alzheimer’s disease (AD). In spite of numerous attempts to prevent the β-amyloidosis, no effective drugs for treating AD have been developed to date. Among many candidate chemicals, methylene blue (MB) has proved its therapeutic potential for AD in a number of in vitro and in vivo studies; but the result of recent clinical trials performed with MB and its derivative was negative. Here, with the aid of multiple photochemical analyses, we first report that photoexcited MB molecules can block Aβ 42 aggregation in vitro . Furthermore, our in vivo study using Drosophila AD model demonstrates that photoexcited MB is highly effective in suppressing synaptic toxicity, resulting in a reduced damage to the neuromuscular junction (NMJ), an enhanced locomotion, and decreased vacuole in the brain. The hindrance effect is attributed to Aβ 42 oxidation by singlet oxygen ( 1 O 2 ) generated from photoexcited MB. Finally, we show that photoexcited MB possess a capability to disaggregate the pre-existing Aβ 42 aggregates and reduce Aβ-induced cytotoxicity. Our work suggests that light illumination can provide an opportunity to boost the efficacies of MB toward photodynamic therapy of AD in future.