Author:
Kondo Takayuki,Yamamoto Tsuyoshi,Okayama Kaoru,Narumi Hideki,Inoue Haruhisa
Abstract
AbstractMicrobial flora is investigated to be related with neuropathological conditions in Alzheimer’s disease (AD), and is attracting attention as a drug discovery resource. However, the relevance between the soil microbiota and the pathological condition has not been fully clarified due to the difficulty in isolation culture and the component complexity. In this study, we established a library of secondly metabolites produced in microorganism to investigate the potential effect of microorganisms on the production of amyloid β (Aβ), one of the most representative pathogens of AD. We conducted a library screening to quantify Aβ and neuronal toxicity by using cortical neurons from human induced pluripotent stem cells (iPSCs) of AD patients after adding secondary metabolites. Screening results and following assessment of dose-dependency identified Verrucarin A, produced in Myrothecium spp., showed 80% decrease in Aβ production. Furthermore, addition of Mer-A2026A, produced in Streptomyces pactum, showed increase in Aβ42/40 ratio at the low concentration, and decrease in Aβ production at the higher concentration. As a result, established library and iPSC-based phenotyping assay clarified a direct link between Aβ production and soil microorganisms. These results suggest that Aβ-microorganism interaction may provide insight into the AD pathophysiology with potential therapeutics.
Funder
Japan Society for the Promotion of Science
the grant for Core Center for iPSC Research of Research Center Network for Realization of Regenerative Medicine from AMED
Publisher
Springer Science and Business Media LLC
Reference38 articles.
1. Fleming, A. On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation of B. influenz? Br. J. Exp. Pathol. 10, 226 (1929).
2. Newman, D. J. & Cragg, G. M. Natural products as sources of new drugs from 1981 to 2014. J. Nat. Prod. 79, 629–661 (2016).
3. Liu, R., Li, X. & Lam, K. S. Combinatorial chemistry in drug discovery. Curr. Opin. Chem. Biol. 38, 117–126 (2017).
4. Li, J. W. H. & Vederas, J. C. Drug discovery and natural products: End of an era or an endless frontier? Science 325, 161–165 (2009).
5. Shen, B. A new golden age of natural products drug discovery. Cell 163, 1297–1300 (2015).
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