Author: Hirano, Shin-ichi ; Terasawa, Tadashi ; Okamura, Kazuhiko ; Watanabe, Yoshio ; Kioka, Tomoyuki ; Yoshioka, Takeo ; Kominato, Kaichiro ; Tone, Hiroshi

A strain of Streptomyces was found to produce new piericidins. The compounds were purified and separated into two substances named Mer-A2026A and B. These new piericidins exhibited vasodilating and depressor activities.

Scientific ReportsQ3 · CROSS-FIELD

Metabolites of soil microorganisms modulate amyloid β production in Alzheimer’s neurons

Q3 · CROSS-FIELD

ArticleOA

Author: Yamamoto, Tsuyoshi ; Inoue, Haruhisa ; Okayama, Kaoru ; Narumi, Hideki ; Kondo, Takayuki

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.

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Indication	Highest Phase	Country/Location	Organization	Date
Hypertension	Preclinical	JP	Mercian Corp.	-

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