Methylene Blue Inhibits Amyloid Aβ Oligomerization by Promoting Fibrillization
Abstract
Amyloid plaques are hallmark neuropathological lesions in Alzheimer's disease, which consist of abnormally aggregated Abeta protein. Multiple Abeta aggregated species have been identified, and neurotoxicity appears to be correlated with the amount of nonfibrillar oligomers. Therefore, selective inhibition of Abeta oligomer formation has emerged as an attractive means of therapeutic intervention. To investigate whether small molecules can modulate aggregation to achieve selective inhibition of neurotoxic amyloid oligomers, Abeta aggregation was assayed in vitro in the presence of methylene blue, using immunoreactivity with the prefibrillar oligomer-specific antibody A11, transmission electron microscopy, and turbidity assays. Methylene blue inhibited oligomerization when used at substoichiometric concentrations relative to that of the Abeta monomer. Inhibition of Abeta oligomerization was achieved concomitant with promotion of fibrillization, suggesting that oligomer and fibril formation are distinct and competing pathways. Methylene blue-mediated promotion of fiber formation occurred via a dose-dependent decrease in the lag time and an increase in the fibrillization rate, consistent with promotion of both filament nucleation and elongation. Addition of methylene blue to preformed oligomers resulted in oligomer loss and promotion of fibrillization. The data show that Abeta oligomer formation is inhibited by promoting fibril formation, which suggests that the relative pathologi…
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Methylene blue and peroxisome proliferator-activated receptor gamma agonists have been reported to have conformation-altering, toxicity-modifying effects similar to those observed after Inpp5d knockdown.
“Methylene blue59 and peroxisome proliferator-activated receptor gamma agonists60 have been reported to have similar conformation-altering, toxicity-modifying effects.”
From Microglial <i>INPP5D</i> limits plaque formation and glial reactivity in the PSAPP mouse model of Alzheimer's disease (2023) · cites this paper as [59]
Increased plaque compaction may be a protective mechanism.
“Increased plaque compaction may be a protective mechanism,59,60”
From Microglial <i>INPP5D</i> limits plaque formation and glial reactivity in the PSAPP mouse model of Alzheimer's disease (2023) · cites this paper as [59]
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Exploring the effects of methylene blue on amyloid fibrillogenesis of lysozyme
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- Authors
- Necula, M., Breydo, L., Milton, S., Kayed, R., van der Veer, W. E., Tone, P., & Glabe, C. G.
- Affiliations
- New York Medical College (US)
- Department of Molecular Biology and Biochemistry, University of California, Irvine, California 92697, Department of Chemistry, University of California, Irvine, California 92697, Department of Medicine, St. Vincent Catholic Medical Centers, Staten Island Division, Staten Island, New York 10310, and New York Medical College, Valhalla, New York 10595
- Corresponding author
- Glabe, Charles G.
- Venue
- Biochemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2007-06-27
- Volume
- 46
- Issue
- 30
- Pages
- 8850-8860
- ISSN
- 0006-2960 (ISSN-L)
- 1520-4995
- OpenAlex
- W2020701897
- Cited by
- 213
- References
- 7
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 4 · 2023: 2 · 2022: 6 · 2021: 10 · 2020: 13 · 2019: 8 · 2018: 11 · 2017: 18 · 2016: 18 · 2015: 7 · 2014: 11 · 2013: 20 · 2012: 20
- FWCI
- 9.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS 31230, R01NS031230)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Keywords
- methylene blue, amyloid-beta, fibrillization, Alzheimer's disease, amyloid plaques, neurotoxicity, fibril nucleation, fibril elongation, time delay
- MeSH terms
- Dose-Response Relationship, Drug, Humans, Kinetics, Methylene Blue, Nephelometry and Turbidimetry, Protein Binding, Protein Denaturation, Recombinant Proteins, Solubility, Amyloid beta-Peptides, Protein Structure, Quaternary, Microscopy, Electron, Transmission, Plaque, Amyloid, In Vitro Techniques
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