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

Byung Il Lee; Yoon Seok Suh; You Jung Chung; Kweon Yu; Chan Beum Park

doi:10.1038/s41598-017-07581-2

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

Sci Rep. 2017 Aug 8;7(1):7523. doi: 10.1038/s41598-017-07581-2.

Authors

Byung Il Lee¹, Yoon Seok Suh^{2

3}, You Jung Chung¹, Kweon Yu^{2

3

4}, Chan Beum Park⁵

Affiliations

¹ KAIST Institute for the BioCentury, Department of Materials Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
² Neurophysiology & Metabolism Research Group, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea.
³ Convergence Research Center for Dementia, Korea Institute of Science and Technology (KIST), Seoul, Korea.
⁴ Department of Functional Genomics, University of Science and Technology, Daejeon, Korea.
⁵ KAIST Institute for the BioCentury, Department of Materials Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea. parkcb@kaist.ac.kr.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease / drug therapy*
Alzheimer Disease / metabolism
Alzheimer Disease / physiopathology
Amyloid beta-Peptides / antagonists & inhibitors*
Amyloid beta-Peptides / chemistry
Amyloid beta-Peptides / metabolism
Amyloidosis / drug therapy*
Amyloidosis / metabolism
Amyloidosis / pathology
Amyloidosis / physiopathology
Animals
Brain / drug effects
Brain / metabolism
Brain / pathology
Disease Models, Animal
Drosophila melanogaster
Humans
Light
Locomotion / drug effects
Locomotion / physiology
Methylene Blue / chemistry
Methylene Blue / pharmacology*
Methylene Blue / radiation effects
Neuromuscular Junction / drug effects
Neuromuscular Junction / metabolism
Neuromuscular Junction / pathology
Neuroprotective Agents / chemistry
Neuroprotective Agents / pharmacology*
Nootropic Agents / chemistry
Nootropic Agents / pharmacology*
Oxidation-Reduction
Peptide Fragments / antagonists & inhibitors*
Peptide Fragments / chemistry
Peptide Fragments / metabolism
Photochemotherapy / methods
Photosensitizing Agents / chemistry
Photosensitizing Agents / pharmacology*
Protein Aggregates / drug effects
Singlet Oxygen / chemistry
Singlet Oxygen / pharmacology

Substances

Amyloid beta-Peptides
Neuroprotective Agents
Nootropic Agents
Peptide Fragments
Photosensitizing Agents
Protein Aggregates
amyloid beta-protein (1-42)
Singlet Oxygen
Methylene Blue