ArticleCell death & disease2020
Sodium butyrate inhibits high cholesterol-induced neuronal amyloidogenesis by modulating NRF2 stabilization-mediated ROS levels: involvement of NOX2 and SOD1.
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 65 citations in OpenAlex.
- Short-chain fatty acid-producing commensals: Key modulators of AD neuroinflammation via the microbiota-gut-brain axis.Current research in microbial sciences · 2026Review
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- Interactions between the gut microbiome and ferroptosis in degenerative diseases: Novel mechanisms and potential therapeutic strategies.Acta pharmaceutica Sinica. B · 2026Review
- Microbiota and Alzheimer's disease: mechanistic insights from a multi-organ perspective.Translational neurodegeneration · 2026Review
- Gut microbiota and metabolites as potential modulators of cognitive impairment after aneurysmal subarachnoid hemorrhage: a hypothesis-driven review.Frontiers in microbiology · 2026Review
- Therapeutic modulation of the gut microbiota by traditional Chinese medicine in the management of cholestatic liver injury.Frontiers in cellular and infection microbiology · 2026Review
- Microbial SCFAs as epigenetic mediators: fine-tuning the gut-brain axis in neurodegenerative disorders.Current research in microbial sciences · 2026Review
- The interplay mechanisms between gut microbiota and ferroptosis in inflammatory bowel disease.Frontiers in immunology · 2026Review
- Review
- The role of microbiota modulation in preventing Alzheimer's disease- a review.Pharmacological reports : PR · 2025Review
- The Gut-Brain Axis in Alzheimer's Disease: Exploring Microbial Influences and Therapeutic Strategies.Molecular neurobiology · 2025Review
- Article
- Multi-omics profiling of dairy cattle oxidative stress identifies hindgut-derived Phascolarctobacterium succinatutens exhibiting antioxidant activity.NPJ biofilms and microbiomes · 2025Article
- From copper homeostasis to cuproptosis: a new perspective on CNS immune regulation and neurodegenerative diseases.Frontiers in neurology · 2025Review
- Harnessing the gut microbiome to modulate ferroptosis: a metabolic strategy for the treatment of digestive tract cancers.Frontiers in immunology · 2025Review
- Baicalein ameliorates DSS-induced ulcerative colitis in mice by inhibiting ferroptosis and regulating gut microbiota.Frontiers in pharmacology · 2025Article
- Immune modulation in inflammatory bowel disease: therapeutic promise of baicalein.Frontiers in pharmacology · 2025Review
- Alleviating D-Galactose-Induced Aging in Mice by Modulating Gut-Liver Axis UsingFoods (Basel, Switzerland) · 2024Article
- Cognitive Function and the Consumption of Probiotic Foods: A National Health and Nutrition Examination Survey Study.Nutrients · 2024Article
- The potential role of gut microbiota-derived metabolites as regulators of metabolic syndrome-associated mitochondrial and endolysosomal dysfunction in Alzheimer's disease.Experimental & molecular medicine · 2024Review
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The gut-brain axis is currently being studied as a therapeutic strategy for neurological diseases, especially Alzheimer's disease (AD). Obesity results in the gut microbiota dysbiosis, which includes butyrate-producing bacteria are reduced. Although sodium butyrate (NaB) has emerged as the potential therapeutic substance in AD, there is a lack of detailed results into what signaling pathways affect amyloidogenesis in AD induced by obesity. Thus, we investigated the regulatory role of NaB on amyloidogenesis in neuronal cells under high cholesterol. In our results, we verified that increased amyloid β peptide (Aβ) accumulation in the brain of obese mice and a reduction in butyrate-producing bacteria due to the gut microbiota dysbiosis induced by obesity. We showed that NaB decreased the expression levels of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) and Aβ accumulation induced by high cholesterol in SK-N-MC cells. We demonstrated that NaB was absorbed in cells through sodium-coupled monocarboxylate transporter 1 (SMCT1) and then inhibited high cholesterol-induced Aβ accumulation. Subsequently, we also observed that reactive oxygen species (ROS) were overproduced because of increased NADPH oxidase 2 (NOX2) expression under high cholesterol. Meanwhile, NaB decreased NOX2 levels through a reduction of NF-κB activity, which ultimately inhibited Aβ accumulation caused by high cholesterol. We demonstrated that NaB increased the expression levels of p21 under high cholesterol, contributing to p21/NRF2 (Nuclear factor erythroid 2-related factor 2) colocalization, which leads to NRF2 stabilization. NRF2 stabilization causes NF-κB inactivation, followed by NOX2 suppression and superoxide dismutase 1 (SOD1) upregulation. Thus, NaB with SOD1 silencing under high cholesterol did not eliminate excessive ROS, and eventually resulted in Aβ accumulation. In conclusion, we demonstrated that NaB prevents excessive ROS through NOX2 suppression and SOD1 upregulation by p21/NRF2 pathway, which is critical for inhibiting BACE1-dependent amyloidogenesis in neuronal cells exposed to high cholesterol environment.
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