ArticleMolecular nutrition & food research2021
Flavan-3-ol Microbial Metabolites Modulate Proteolysis in Neuronal Cells Reducing Amyloid-beta (1-42) Levels.
Article in Molecular nutrition & food research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 36 citations in OpenAlex.
- The Role of Lipoprotein and Gut Microbiome in Alzheimer's Disease: A Review of Novel Findings and Potential Applications.Current Alzheimer research · 2026Review
- Polyphenols Bioactive Metabolites, and Their Anti-Biofilm and Neuroprotective Potential.Foods (Basel, Switzerland) · 2025Review
- Article
- From the gut to the brain: the long journey of phenolic compounds with neurocognitive effects.Nutrition reviews · 2025Review
- Microbiome-targeted Alzheimer's interventions via gut-brain axis.Frontiers in microbiology · 2025Review
- Article
- Using Targeted Metabolomics to Unravel Phenolic Metabolites of Plant Origin in Animal Milk.International journal of molecular sciences · 2024Article
- Ginsenosides Rg1 and Rg2 Activate Autophagy and Attenuate Oxidative Stress in Neuroblastoma Cells Overexpressing Aβ(1-42).Antioxidants (Basel, Switzerland) · 2024Article
- Therapeutics for neurodegenerative diseases by targeting the gut microbiome: from bench to bedside.Translational neurodegeneration · 2024Review
- The Role of Cysteine Protease Cathepsins B, H, C, and X/Z in Neurodegenerative Diseases and Cancer.International journal of molecular sciences · 2023Review
- Dietary Phenolic Compounds: Their Health Benefits and Association with the Gut Microbiota.Antioxidants (Basel, Switzerland) · 2023Review
- The Potential of Flavonoids and Flavonoid Metabolites in the Treatment of Neurodegenerative Pathology in Disorders of Cognitive Decline.Antioxidants (Basel, Switzerland) · 2023Review
- A Novel Strategy for Alzheimer's Disease Based on the Regulatory Effect of Amyloid-β on Gut Flora.Journal of Alzheimer's disease : JAD · 2023Review
- Metabolic Fate of Orally Ingested Proanthocyanidins through the Digestive Tract.Antioxidants (Basel, Switzerland) · 2022Review
- Targeting Proteolysis with Cyanogenic Glycoside Amygdalin Induces Apoptosis in Breast Cancer Cells.Molecules (Basel, Switzerland) · 2022Article
- Cellular Antioxidant Effect of an Aronia Extract and Its Polyphenolic Fractions Enriched in Proanthocyanidins, Phenolic Acids, and Anthocyanins.Antioxidants (Basel, Switzerland) · 2022Article
- Flavanols from Nature: A Phytochemistry and Biological Activity Review.Molecules (Basel, Switzerland) · 2022Review
- Flavan-3-ol Microbial Metabolites Modulate Proteolysis in Neuronal Cells Reducing Amyloid-beta (1-42) Levels.Molecular nutrition & food research · 2021Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionAlzheimer's disease (AD) is a progressive neurodegeneration characterized by extensive protein aggregation and deposition in the brain, associated with defective proteasomal and autophagic-lysosomal proteolytic pathways. Since current drugs can only reduce specific symptoms, the identification of novel treatments is a major concern in AD research. Among natural compounds, (poly)phenols and their derivatives/metabolites are emerging as candidates in AD prevention due to their multiple beneficial effects. This study aims to investigate the ability of a selection of phenyl-γ-valerolactones, gut microbiota-derived metabolites of flavan-3-ols, to modulate the functionality of cellular proteolytic pathways. METHODS AND
resultsNeuronal SH-SY5Y cells transfected with either the wild-type or the 717 valine-to-glycine amyloid precursor protein mutated gene are used as an AD model and treated with 5-(4'-hydroxyphenyl)-γ-valerolactone, 5-(3',4'-dihydroxyphenyl)-γ-valerolactone and 5-(3'-hydroxyphenyl)-γ-valerolactone-4'-sulfate. Combining in vitro and in silico studies, it is observed that the phenyl-γ-valerolactones of interest modulated cellular proteolysis via proteasome inhibition and consequent autophagy upregulation and inhibited cathepsin B activity, eventually reducing the amount of intra- and extracellular amyloid-beta (1-42) peptides.
conclusionThe findings of this study establish, for the first time, that these metabolites exert a neuroprotective activity by regulating intracellular proteolysis and confirm the role of autophagy and cathepsin B as possible targets of AD preventive/therapeutic strategies.
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