Molecular Mechanisms of Neuroprotection by Ketone Bodies and Ketogenic Diet in Cerebral Ischemia and Neurodegenerative Diseases

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 25(1), P. 124 - 124

Published: Dec. 21, 2023

Ketone bodies (KBs), such as acetoacetate and β-hydroxybutyrate, serve crucial alternative energy sources during glucose deficiency. KBs, generated through ketogenesis in the liver, are metabolized into acetyl-CoA extrahepatic tissues, entering tricarboxylic acid cycle electron transport chain for ATP production. Reduced metabolism mitochondrial dysfunction correlate with increased neuronal death brain damage cerebral ischemia neurodegeneration. Both KBs ketogenic diet (KD) demonstrate neuroprotective effects by orchestrating various cellular processes metabolic signaling functions. They enhance function, mitigate oxidative stress apoptosis, regulate epigenetic post-translational modifications of histones non-histone proteins. Additionally, KD contribute to reducing neuroinflammation modulating autophagy, neurotransmission systems, gut microbiome. This review aims explore current understanding molecular mechanisms underpinning against neurodegenerative diseases, including Alzheimer’s disease Parkinson’s disease.

Language: Английский

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Association of DNA methylation/demethylation with the functional outcome of stroke in a hyperinflammatory state

Neural Regeneration Research, Journal Year: 2024, Volume and Issue: 19(10), P. 2229 - 2239

Published: Jan. 8, 2024

JOURNAL/nrgr/04.03/01300535-202410000-00024/figure1/v/2024-02-06T055622Z/r/image-tiff Inflammation is closely related to stroke prognosis, and high inflammation status leads poor functional outcome in stroke. DNA methylation involved the pathogenesis prognosis of However, effect on at levels unclear. In this study, we constructed a hyperinflammatory cerebral ischemia mouse model investigated hypomethylation hypermethylation outcome. We transient middle artery occlusion treated mice with lipopolysaccharide induce state. To investigate stroke, used small molecule inhibitors restrain function key demethylation enzymes. 2,3,5-Triphenyltetrazolium chloride staining, neurological scores, neurobehavioral tests, enzyme-linked immunosorbent assay, quantitative reverse transcription PCR western blot assay were evaluate effects after mice. assessed changes global by measuring 5-mc 5-hmc peripheral blood use inhibitor. group inhibitor, brain tissue 2,3,5-triphenyltetrazolium staining showed an increase infarct volume, which was accompanied decrease scores worsening performance. The inflammatory factors interleukin 6 interleukin-1 beta ischemic plasma elevated, indicating increased inflammation. Related pathway exploration significant overactivation nuclear factor kappa B. These results suggested that inhibiting led following Further, reversed inhibition demethylation. Our findings suggest regulates response has important role

Language: Английский

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Polymeric nanocomposite electrode for enhanced electrochemical detection of α-lipoic acid: Application in neuroinflammation prevention and clinical analysis

Environmental Research, Journal Year: 2023, Volume and Issue: 245, P. 117369 - 117369

Published: Oct. 10, 2023

Language: Английский

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Association between niacin intake and knee osteoarthritis pain and function: a longitudinal cohort study

Clinical Rheumatology, Journal Year: 2024, Volume and Issue: 43(2), P. 753 - 764

Published: Jan. 5, 2024

Language: Английский

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The role of the gut microbiome in disorders of gut–brain interaction

FEBS Journal, Journal Year: 2024, Volume and Issue: unknown

Published: June 23, 2024

Disorders of Gut‐Brain Interaction (DGBI) are widely prevalent and commonly encountered in gastroenterology practice. While several peripheral central mechanisms have been implicated the pathogenesis DGBI, a recent body work suggests an important role for gut microbiome. In this review, we highlight how microbiota their metabolites affect physiologic changes underlying symptoms with particular focus on mechanistic influence GI transit, visceral sensitivity, intestinal barrier function secretion, CNS processing. This review emphasizes complexity local distant effects microbial physiological function, influenced by factors such as metabolite concentration, duration exposure, receptor location, host genetics, disease state. Large‐scale vitro has elucidated interactions between receptors metabolome but there is need future research to integrate preclinical findings clinical studies. The development novel, targeted therapeutic strategies DGBI hinges deeper understanding these metabolite‐host interactions, offering exciting possibilities treatment DGBI.

Language: Английский

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Association between niacin intake and osteoarthritis in the US population based on NHANES 1999–2018

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 22, 2025

The relationship between niacin and osteoarthritis (OA) is not clear. Using a retrospective cohort study from the National Health Nutrition Examination Survey (NHANES), this aimed to investigate association intake osteoarthritis. This conducted cross-sectional analysis using data 1999–2018 was assessed univariate multivariate weighted logistic regression models restricted cubic spline curves (RCS). Nonlinear correlation analyzed by fitting smooth curve. In study, 30,620 participants were examined, with 1,864 individuals diagnosed osteoarthritis, resulting in prevalence of 5.74%. Utilizing regression, consistent inverse Niacin observed (OR = 0.99, 95% CI: 0.98–0.99, P 0.003). When treated as categorical variable, highest quartile (Q4) exhibited 33% reduced risk compared lowest (Q1) 0.67, 0.53–0.83, 0.0004). revealed non-linear (non-linear 0.022), 33.53 inflection point. Subgroup analyses further highlighted stronger Non − Hispanic Black other Race patients. results showed negative linear OA risk. By increasing niacin-rich foods, can be reduced, providing ideas for prevention treatment Further future studies are recommended validate our findings.

Language: Английский

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β-Hydroxybutyrate Regulates Activated Microglia to Alleviate Neurodegenerative Processes in Neurological Diseases: A Scoping Review

Nutrients, Journal Year: 2023, Volume and Issue: 15(3), P. 524 - 524

Published: Jan. 19, 2023

This scoping review aimed to summarise the effects of ketone body β-hydroxybutyrate. The details revealed pathways and functional properties following its intervention in context neurodegenerative diseases. In this study, 5 research publications that met inclusion exclusion criteria were shortlisted. Following intervention, we discovered a tendency reduced inflammatory status microglia, as evidenced by lower levels pro-inflammatory mediators produced, microgliosis afflicted tissues, enhanced cognitive functions models. We found there is significant overlap mechanism action β-hydroxybutyrate (BHB) via activation G-protein-Coupled Receptor 109A (GPR109a) receptor deactivation inflammasome complex. Furthermore, although comparing outcomes can be challenging due heterogeneity study model, results have assembled here consistent, giving us confidence intervention’s efficacy. also discussed new studies where BHB involved various roles regulating inflammation allowing for fresh therapeutic targets against neurodegeneration. brief provides evidence support huge potential treatment illnesses.

Language: Английский

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Structural basis of hydroxycarboxylic acid receptor signaling mechanisms through ligand binding

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Sept. 22, 2023

Abstract Hydroxycarboxylic acid receptors (HCA) are expressed in various tissues and immune cells. HCA2 its agonist thus important targets for treating inflammatory metabolic disorders. Only limited information is available, however, on the active-state binding of HCAs with agonists. Here, we present cryo-EM structures human HCA2-Gi HCA3-Gi signaling complexes multiple compounds bound. Agonists were revealed to form a salt bridge arginine, which conserved HCA family, activate these receptors. Extracellular regions lid-like structure that covers ligand-binding pocket. Although transmembrane (TM) 6 undergoes dynamic conformational changes, ligands do not directly interact amino acids TM6, suggesting indirect induces slight shift TM6 Gi proteins. Structural analyses agonist-bound HCA3 together mutagenesis molecular dynamics simulation provide insights into ligand recognition activation mechanisms.

Language: Английский

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NLRP3/1-mediated pyroptosis: beneficial clues for the development of novel therapies for Alzheimer’s disease

Neural Regeneration Research, Journal Year: 2023, Volume and Issue: 19(11), P. 2400 - 2410

Published: Dec. 21, 2023

The inflammasome is a multiprotein complex involved in innate immunity that mediates the inflammatory response leading to pyroptosis, which lytic, form of cell death. There accumulating evidence nucleotide-binding domain and leucine-rich repeat pyrin containing 3 (NLRP3) inflammasome-mediated microglial pyroptosis NLRP1 neuronal brain are closely associated with pathogenesis Alzheimer’s disease. In this review, we summarize possible pathogenic mechanisms disease, focusing on neuroinflammation. We also describe structures NLRP3 role their activation plays Finally, examine neuroprotective activity small-molecule inhibitors, endogenous inhibitor proteins, microRNAs, natural bioactive molecules target NLRP1, based rationale inhibiting can be an effective therapeutic strategy for

Language: Английский

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Parkinson’s Disease Gene Biomarkers Screened by the LASSO and SVM Algorithms

Brain Sciences, Journal Year: 2023, Volume and Issue: 13(2), P. 175 - 175

Published: Jan. 20, 2023

Parkinson's disease (PD) is a common progressive neurodegenerative disorder. Various evidence has revealed the possible penetration of peripheral immune cells in substantia nigra, which may be essential for PD. Our study uses machine learning (ML) to screen potential PD genetic biomarkers. Gene expression profiles were screened from Expression Omnibus (GEO). Differential genes (DEGs) selected enrichment analysis. A protein-protein interaction (PPI) network was built with STRING database (Search Tool Retrieval Interacting Genes), and two ML approaches, namely least absolute shrinkage selection operator (LASSO) support vector recursive feature elimination (SVM-RFE), employed identify candidate genes. The external validation dataset further tested degree diagnostic value To assess validity diagnosis, we determined receiver operating characteristic (ROC) curve. convolution tool evaluate composition by CIBERSORT, performed correlation analyses on basis training dataset. Twenty-seven DEGs control samples. results analysis showed close association inflammatory immune-associated diseases. Both LASSO SVM algorithms eight six AGTR1, GBE1, TPBG, HSPA6 are overlapping hub strongly related area under ROC (AUC), including AGTR1 (AUC = 0.933), GBE1 0.967), TPBG 0.767), 0.633), suggested that these have good value, significantly associated cell infiltration. identified as biomarkers diagnosis provide novel viewpoint mechanism therapy.

Language: Английский

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