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Neuroprotective effects of mushroom biomass digestive fractions and gut microbiota metabolites in microglial and Caenorhabditis elegans models of neurodegeneration

2025-12-10Artigo de investigação Acesso aberto
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dc.contributor.authorAraújo-Rodrigues, Helena
dc.contributor.authorGarzón-García, Lidia
dc.contributor.authorSalsinha, Ana Sofia
dc.contributor.authorRelvas, João Bettencourt
dc.contributor.authorTavaria, Freni K.
dc.contributor.authorSantos-Buelga, Celestino
dc.contributor.authorGonzález-Paramás, Ana M.
dc.contributor.authorPintado, Manuela E.
dc.date.accessioned2026-01-13T11:02:43Z
dc.date.available2026-01-13T11:02:43Z
dc.date.issued2025-12-10
dc.description.abstractBackground: The accumulation of ?-amyloid plaques, neurofibrillary tangles, and neuroinflammation are key hallmarks of Alzheimer’s disease (AD). Reactive oxygen species (ROS) act as major triggers and amplifiers of neuroinflammatory responses, contributing to immune dysregulation and neuronal damage. Despite extensive research, no effective therapy halts or reverses AD progression, emphasizing the need for alternative preventive strategies, including the use of natural compounds. Objectives: This study evaluated the neuroprotective effects of simulated digestive fractions (permeate fraction) of mushroom biomass (MB)—Trametes versicolor (TV), Hericium erinaceus (HE), and Pleurotus ostreatus (PO)—and key gut microbiota-derived metabolites, such as short-chain fatty acids (SCFAs) and ?-aminobutyric acid (GABA) on ROS production in human microglial cells (HMC3) and in transgenic Caenorhabditis elegans models exhibiting hyperphosphorylated Tau and ?-amyloid-induced toxicity. Methods: Cell viability and ROS production were assessed in HMC3 cells treated with mushroom fractions and metabolites. Chemotaxis and paralysis assays were performed in transgenic C. elegans strains expressing hyperphosphorylated Tau or ?-amyloid proteins. Results: Mushroom digestive fractions and SCFAs significantly decreased ROS levels in HMC3 cells. Moreover, mushroom digestive fractions, butyric acid, and GABA improved behavioral outcomes in C. elegans, enhancing chemotaxis and delaying paralysis. These effects were dose-dependent and varied among mushroom species and metabolites. Conclusions: Mushroom-derived digestive fractions and microbiota-related metabolites exhibit neuroprotective activity by modulating oxidative stress and mitigating neurodegeneration-associated behaviors. Diets enriched with such MBs may support preventive strategies for neurodegenerative diseases. Further research is required to elucidate the molecular mechanisms underlying these protective effects and their translational potential for human neurodegenerative diseases.eng
dc.identifier.citationAraújo-Rodrigues, H., Garzón-García, L., Salsinha, A. S., & Relvas, J. B. et al. (2025). Neuroprotective effects of mushroom biomass digestive fractions and gut microbiota metabolites in microglial and caenorhabditis elegans models of neurodegeneration. Nutrients, 17(24), Article 3867. https://doi.org/10.3390/nu17243867
dc.identifier.doi10.3390/nu17243867
dc.identifier.eid105026098957
dc.identifier.issn2072-6643
dc.identifier.other526eb183-193c-4618-8232-99d0cbf4a974
dc.identifier.pmcPMC12735695
dc.identifier.pmid41470813
dc.identifier.urihttp://hdl.handle.net/10400.14/56507
dc.identifier.wos001647127200001
dc.language.isoeng
dc.peerreviewedyes
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectCaenorhabditis elegans
dc.subjectChemotaxis and paralysis experiment
dc.subjectHuman microglial cell line (HMC3)
dc.subjectHyperphosphorylated Tau and amyloid toxicity
dc.subjectMushroom biomass
dc.subjectNeuroprotective effects
dc.subjectROS production
dc.titleNeuroprotective effects of mushroom biomass digestive fractions and gut microbiota metabolites in microglial and Caenorhabditis elegans models of neurodegenerationeng
dc.typeresearch article
dspace.entity.typePublication
oaire.citation.issue24
oaire.citation.titleNutrients
oaire.citation.volume17
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85

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