(ORDO NEWS) — Japanese researchers have shown that organic compounds released by soil microorganisms affect the formation of amyloid plaques in neurons. They can form the basis for preventive or therapeutic drugs for Alzheimer’s disease.
Alzheimer’s disease is the most common form of dementia, affecting about 50 million people worldwide. Recent studies have shown that beta-amyloid peptides, one of the pathogenic factors in Alzheimer’s disease, may be a natural immune response to pathogens. There is also evidence that the gut or oral microbiota is able to regulate this disease.
In addition, about 60% of the small molecule therapeutic agents on the market are derived from natural products, so secondary metabolites produced by microorganisms are important in the development of therapeutic drugs. And because of the difficulties in cultivation, soil microorganisms are the least studied group.
In their work, the scientists created a library of 98 secondary metabolites – organic compounds that are not involved in the growth, development or reproduction – of soil microorganisms.
To find out how these molecules affect the development of Alzheimer’s disease, the authors of the article reprogrammed the somatic cells of patients into neurons of the cerebral cortex and added secondary metabolites to their cultivation medium.
In each experiment, the amount of beta-amyloid Aβ42 responsible for the formation of amyloid plaques was measured, as well as its level in relation to the harmless form of Aβ40. The researchers found that verrucarin A is a secondary metabolite produced by the fungus Myrothecium spp.
Reduces the amount of both Aβ42 and Aβ40 amyloid. Another secondary metabolite, Mer-A2026A, produced by Streptomyces pactum , affected neurons in a dose-dependent manner: at moderate amounts, it reduced both beta-amyloid levels, but at higher concentrations, it increased Aβ42 levels.
The results of the work show how the study of metabolites produced by microorganisms using stem cells can lead to the creation of new therapeutic agents for the treatment of neurodegenerative diseases.
So far, researchers cannot transfer the results to what is happening directly in the brain, since there is no direct evidence that the studied substances are present in it at the studied concentrations. Experiments using animal models will help to better understand the relationship between Alzheimer’s disease and the vital activity of microorganisms.
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