A Food and Drug Administration-approved Asthma Therapeutic Agent Impacts Amyloid β in the Brain in a Transgenic Model of Alzheimer Disease*

Background: 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. 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.

• Publication year

  2014

• Venue

  Journal of Biological Chemistry

• Publication date

  2014-12-02

• Fields of study

  Medicine

• Identifiers
  DOI 10.1074/jbc.M114.586602PMID 25468905PMCID PMC4303653
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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