A Food and Drug Administration-approved Asthma Therapeutic Agent Impacts Amyloid β in the Brain in a Transgenic Model of Alzheimer Disease
Open accessAbstract
Interfering with the assembly of Amyloid β (Aβ) peptides from monomer to oligomeric species and fibrils or promoting their clearance from the brain are targets of anti-Aβ-directed therapies in Alzheimer disease. Here we demonstrate that cromolyn sodium (disodium cromoglycate), a Food and Drug Administration-approved drug already in use for the treatment of asthma, efficiently inhibits the aggregation of Aβ monomers into higher-order oligomers and fibrils in vitro without affecting Aβ production. In vivo , the levels of soluble Aβ are decreased by over 50% after only 1 week of daily intraperitoneally administered cromolyn sodium. Additional in vivo microdialysis studies also show that this compound decreases the half-life of soluble Aβ in the brain. These data suggest a clear effect of a peripherally administered, Food and Drug Administration-approved medication on Aβ economy, supporting further investigation of the potential long-term efficacy of cromolyn sodium in Alzheimer disease.Cromolyn sodium is an FDA-approved drug structurally similar to fisetin, an antiamyloidogenic molecule. Results Cromolyn sodium interferes with amyloid β (Aβ) aggregation in vitro while rapidly decreasing the levels of soluble Aβ peptides in vivo after a week. Conclusion Cromolyn sodium may have an impact on amyloid economy. Significance Developing new disease-modifying therapeutics remains an urgent need in the treatment of Alzheimer disease.
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Adding masupirdine (SUVN-502) as adjuvant to donepezil and memantine demonstrated no additional palliative benefits in a phase 2 clinical trial (NCT02580305).
“However, adding the 5-HT6 receptor antagonist, masupirdine (SUVN-502), as adjuvant to donepezil and memantine, demonstrated no additional palliative benefits in a phase 2 clinical trial (NCT02580305) [58, 59].”
From Current therapeutics for Alzheimer’s disease and clinical trials (2024) · cites this paper as [59]
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“For asthma treatment, cromolyn sodium powder is micronized for inhalation to the lungs via dry powder inhaler, whereas liquid intranasal and ophthalmic formulations have also been developed for the treatment of rhinitis and conjunctivitis (42).”
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“Using a split-luciferase complementation method to specifically monitor oligomer formation (32), we observed that treatment of HEK293 cells overexpressing both N- or C-terminal of luciferase conjugated A 42 with cromolyn sodium significantly decreased the luminescence signal in a dose-dependent manner, therefore demon…”
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Self-citation
- Authors
- Hori, Y., Takeda, S., Cho, H., Wegmann, S., Shoup, T. M., Takahashi, K., Irimia, D., Elmaleh, D. R., Hyman, B. T., & Hudry, E.
- Affiliations
- Massachusetts General Hospital (US)
- Harvard University (US)
- ORCID
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2015-01
- Volume
- 290
- Issue
- 4
- Pages
- 1966-1978
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC4303653
- OpenAlex
- W1965296579
- Cited by
- 78
- References
- 54
- Citations by year
- 2026: 6 · 2025: 1 · 2024: 8 · 2023: 5 · 2022: 14 · 2021: 10 · 2020: 5 · 2019: 6 · 2018: 9 · 2017: 8 · 2016: 2 · 2015: 4
- FWCI
- 3.11
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (26893042)
- National Institute on Aging (P50AG005134, P30AG062421)
- National Institute of Neurological Disorders and Stroke (P30NS045776)
- National Institute of Biomedical Imaging and Bioengineering (P41EB002503)
- 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
- disodium cromoglycate, amyloid-beta, Alzheimer's disease, amyloid aggregation inhibition, transgenic mouse model, microdialysis, disease-modifying therapy
- MeSH terms
- Alzheimer Disease, Animals, Brain, Cells, Cultured, Disease Models, Animal, Cromolyn Sodium, Flavonoids, Humans, Mice, Transgenic, Peptide Fragments, United States, United States Food and Drug Administration, Amyloid beta-Peptides, Drug Approval, Microglia, Flavonols, Microscopy, Electron, Transmission, Mice
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