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Neuroprotective effects of mushroom biomass digestive fractions and gut microbiota metabolites in microglial and Caenorhabditis elegans models of neurodegeneration
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Resumo(s)
Background: 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.
Descrição
Palavras-chave
Caenorhabditis elegans Chemotaxis and paralysis experiment Human microglial cell line (HMC3) Hyperphosphorylated Tau and amyloid toxicity Mushroom biomass Neuroprotective effects ROS production
Contexto Educativo
Citação
Araújo-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