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

Abstract 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 the...

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Autores principales: Byung Il Lee, Yoon Seok Suh, You Jung Chung, Kweon Yu, Chan Beum Park
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Lenguaje:EN
Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/78393ed14b9b4175b0ea585ab056fff5
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spelling oai:doaj.org-article:78393ed14b9b4175b0ea585ab056fff52021-12-02T11:52:57ZShedding Light on Alzheimer’s β-Amyloidosis: Photosensitized Methylene Blue Inhibits Self-Assembly of β-Amyloid Peptides and Disintegrates Their Aggregates10.1038/s41598-017-07581-22045-2322https://doaj.org/article/78393ed14b9b4175b0ea585ab056fff52017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07581-2https://doaj.org/toc/2045-2322Abstract 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 Aβ42 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 Aβ42 oxidation by singlet oxygen (1O2) generated from photoexcited MB. Finally, we show that photoexcited MB possess a capability to disaggregate the pre-existing Aβ42 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.Byung Il LeeYoon Seok SuhYou Jung ChungKweon YuChan Beum ParkNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Byung Il Lee
Yoon Seok Suh
You Jung Chung
Kweon Yu
Chan Beum Park
Shedding Light on Alzheimer’s β-Amyloidosis: Photosensitized Methylene Blue Inhibits Self-Assembly of β-Amyloid Peptides and Disintegrates Their Aggregates
description Abstract 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 Aβ42 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 Aβ42 oxidation by singlet oxygen (1O2) generated from photoexcited MB. Finally, we show that photoexcited MB possess a capability to disaggregate the pre-existing Aβ42 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.
format article
author Byung Il Lee
Yoon Seok Suh
You Jung Chung
Kweon Yu
Chan Beum Park
author_facet Byung Il Lee
Yoon Seok Suh
You Jung Chung
Kweon Yu
Chan Beum Park
author_sort Byung Il Lee
title Shedding Light on Alzheimer’s β-Amyloidosis: Photosensitized Methylene Blue Inhibits Self-Assembly of β-Amyloid Peptides and Disintegrates Their Aggregates
title_short Shedding Light on Alzheimer’s β-Amyloidosis: Photosensitized Methylene Blue Inhibits Self-Assembly of β-Amyloid Peptides and Disintegrates Their Aggregates
title_full Shedding Light on Alzheimer’s β-Amyloidosis: Photosensitized Methylene Blue Inhibits Self-Assembly of β-Amyloid Peptides and Disintegrates Their Aggregates
title_fullStr Shedding Light on Alzheimer’s β-Amyloidosis: Photosensitized Methylene Blue Inhibits Self-Assembly of β-Amyloid Peptides and Disintegrates Their Aggregates
title_full_unstemmed Shedding Light on Alzheimer’s β-Amyloidosis: Photosensitized Methylene Blue Inhibits Self-Assembly of β-Amyloid Peptides and Disintegrates Their Aggregates
title_sort shedding light on alzheimer’s β-amyloidosis: photosensitized methylene blue inhibits self-assembly of β-amyloid peptides and disintegrates their aggregates
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/78393ed14b9b4175b0ea585ab056fff5
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