Decoding microglial immunometabolism: a new frontier in Alzheimer's disease research

Molecular Neurodegeneration, Journal Year: 2025, Volume and Issue: 20(1)

Published: March 27, 2025

Abstract Alzheimer’s disease (AD) involves a dynamic interaction between neuroinflammation and metabolic dysregulation, where microglia play central role. These immune cells undergo reprogramming in response to AD-related pathology, with key genes such as TREM2, APOE, HIF-1α orchestrating these processes. Microglial metabolism adapts environmental stimuli, shifting oxidative phosphorylation glycolysis. Hexokinase-2 facilitates glycolytic flux, while AMPK acts an energy sensor, coordinating lipid glucose metabolism. TREM2 APOE regulate microglial homeostasis, influencing Aβ clearance responses. LPL ABCA7, both associated AD risk, modulate processing cholesterol transport, linking neurodegeneration. PPARG further supports by regulating inflammatory Amino acid also contributes function. Indoleamine 2,3-dioxygenase controls the kynurenine pathway, producing neurotoxic metabolites linked pathology. Additionally, glucose-6-phosphate dehydrogenase regulates pentose phosphate maintaining redox balance activation. Dysregulated metabolism, influenced genetic variants APOE4, impair responses exacerbate progression. Recent findings highlight interplay regulators like REV-ERBα, which modulates inflammation, Syk, influences clearance. insights offer promising therapeutic targets, including strategies aimed at modulation, could restore function depending on stage. By integrating metabolic, immune, factors, this review underscores importance of immunometabolism AD. Targeting pathways provide novel for mitigating restoring function, ultimately paving way innovative treatments neurodegenerative diseases.

Language: Английский

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Protective effects of ginsenoside Rd on inflammation and mitochondrial dysfunction in lipopolysaccharide-induced microglial activation through histone deacetylase 5-mediated signaling

Food Bioscience, Journal Year: 2025, Volume and Issue: unknown, P. 106248 - 106248

Published: Feb. 1, 2025

Language: Английский

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Vicenin-2 Hinders Pro-Inflammatory Response via Targeting the CaMKKβ-AMPK-SIRT1 Axis in Lipopolysaccharide-Stressed THP-1 Cells

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 2077 - 2077

Published: Feb. 27, 2025

Plant secondary metabolites are known to be valuable agents hamper inflammation owing their multiple mechanisms of action. This study investigates the molecular underlying anti-inflammatory effects vicenin-2 in lipopolysaccharide (LPS)-stressed THP-1 cells. After ascertaining safety our vitro model, we assessed potential this flavonoid. Indeed, it counteracted increase tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 levels, as well overexpression both inducible nitric oxide synthase (iNOS) cyclooxygenase (COX)-2 caused by exposure cells LPS. Acknowledged role SIRT1 inflammatory process, focused attention on enzyme. Our results showed that LPS dramatically decreased expression SIRT1, whereas restored levels enzyme those unexposed These were also observed terms acetylated p53, a substrate. Notably, did not act direct activator SIRT1. Therefore, investigated involvement AMP-activated protein kinase (AMPK), an upstream Of note, blocking AMPK dorsomorphin, protective activity lost, suggesting engagement kinase. Consequently, blockage downstream loss effect vicenin-2, which was no longer able decrease activation nuclear (NF)-κB production cytokines induced Finally, docking simulation suggested might Ca2+/calmodulin-dependent β (CaMKKβ), one regulators AMPK. Overall, suggest may due interaction with CaMKKβ-AMPK-SIRT1 axis.

Language: Английский

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Single local delivery of 5′‐(N‐ethylcarboxamido)adenosine depots ameliorates myocardial infarction‐induced cardiac dysfunction via the enhancement of mitostasis

View, Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

Abstract Myocardial infarction (MI) stands as a prominent contributor to global mortality. Despite existing therapies, there are notable shortcomings in delivering optimal cardiac support and reversing pathological progression, particularly within early stages. Adenosine presents promising therapeutic target; however, its clinical utility is impeded by inherent limitations. In this study, an advanced strategy using adenosine agonist pioneered ameliorate MI‐induced myocardial damage. Herein, derivative 5′‐(N‐ethylcarboxamido) (NECA) employed, efficacy evaluated via single local delivery into infarcted myocardium following MI. NECA displays remarkable benefits endothelial cells cardiomyocytes under both normoxic hypoxic conditions. Likewise, localized newly developed NECA‐loaded micro‐depots demonstrates improvement function prevention of damage MI mouse model, with promotion angiogenesis suppression inflammation, oxidation, apoptosis. Mechanistically, exerts the enhancement mitostasis triggering AMP‐activated protein kinase α (AMPKα) phosphorylation Peroxisome proliferator‐activated receptor gamma coactivator 1‐alpha(PGC‐1α) activation. These findings highlight significance recovery, single‐delivered depots providing intervention for individuals critically severe phase.

Language: Английский

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Sitagliptin regulates the AMPK/NF-κB signaling pathway to alleviate lipopolysaccharide-induced inflammatory responses and promote osteogenic differentiation in rat bone marrow mesenchymal stem cells

Archives of Oral Biology, Journal Year: 2025, Volume and Issue: unknown, P. 106253 - 106253

Published: April 1, 2025

This study aimed to explore the impact of sitagliptin on inflammatory response and osteogenic differentiation in lipopolysaccharide (LPS)-stimulated rat bone marrow mesenchymal stem cells (BMSCs) clarify underlying mechanisms action. In vitro-cultured BMSCs were identified, treated with a range doses, assessed cell counting kit-8 assay quantify viability. The expression proteins genes relevant inflammation osteogenesis was measured using enzyme-linked immunosorbent real-time quantitative polymerase chain reaction techniques. ability analyzed by alkaline phosphatase staining, activity assay, alizarin red s staining. Adenosine monophosphate-activated protein kinase (AMPK)/nuclear factor-kappa B (NF-κB) signaling pathway activation detected through western blotting. High but not low concentrations significantly suppressed cellular Sitagliptin dose-dependently inhibited LPS-induced responses while facilitating their differentiation. It also activated AMPK suppressing NF-κB activity. inhibitor treatment partially reversed these beneficial effects osteogenesis. suppresses promoting modulation AMPK/NF-κB activity, thereby mitigating functional impairment under microenvironmental conditions.

Language: Английский

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Therapeutic potential of natural flavonoids in atherosclerosis through endothelium-protective mechanisms: An update

Pharmacology & Therapeutics, Journal Year: 2025, Volume and Issue: unknown, P. 108864 - 108864

Published: April 1, 2025

Language: Английский

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Inflammasome activity regulation by PUFA metabolites

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Sept. 3, 2024

Oxidative stress and the accompanying chronic inflammation constitute an important metabolic problem that may lead to pathology, especially when body is exposed physicochemical biological factors, including UV radiation, pathogens, drugs, as well endogenous disorders. The cellular response associated, among others, with changes in lipid metabolism, mainly due oxidation action of lipolytic enzymes. Products oxidative fragmentation/cyclization polyunsaturated fatty acids (PUFAs) [4-HNE, MDA, 8-isoprostanes, neuroprostanes] eicosanoids generated a result enzymatic metabolism PUFAs significantly modify functioning immune system by interfering intracellular molecular signaling. key regulators inflammation, effectiveness which can be regulated interacting products under stress, are inflammasome complexes. An example both negative or positive regulation NLRP3 activity 4-HNE depending on severity stress. modifies direct interaction alteration NF-κB Furthermore, prostaglandin E2 known positively correlated NLRC4 activity, while its potential interference AIM2 NLRP1 unproven. Therefore, influence PUFA metabolites well-characterized complexes reviewed.

Language: Английский

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Exploring the Interconnection between Metabolic Dysfunction and Gut Microbiome Dysbiosis in Osteoarthritis: A Narrative Review

Biomedicines, Journal Year: 2024, Volume and Issue: 12(10), P. 2182 - 2182

Published: Sept. 25, 2024

Osteoarthritis (OA) is a prevalent joint disorder and the most common form of arthritis, affecting approximately 500 million people worldwide, or about 7% global population. Its pathogenesis involves complex interplay between metabolic dysfunction gut microbiome (GM) alterations. This review explores relationship disorders-such as obesity, diabetes, dyslipidemia-and OA, highlighting their shared risk factors, including aging, sedentary lifestyle, dietary habits. We further explore role GM dysbiosis in elucidating how systemic inflammation, oxidative stress, immune dysregulation driven by altered microbial metabolites contribute to OA progression. Additionally, concept "leaky syndrome" discussed, illustrating compromised barrier function exacerbates local inflammation. Therapeutic strategies targeting composition, lifestyle interventions, pharmacological non-pharmacological microbiota-targeted therapies, are reviewed for potential mitigate Future research directions emphasize importance identifying novel biomarkers treatment response, adopting personalized approaches, integrating multiomics data enhance our understanding metabolic-GM-OA connection advance precision medicine management.

Language: Английский

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Protective, Anti-Inflammatory, and Anti-Aging Effects of Soy Isoflavones on Skin Cells: An Overview of In Vitro and In Vivo Studies

Molecules, Journal Year: 2024, Volume and Issue: 29(23), P. 5790 - 5790

Published: Dec. 7, 2024

Isoflavones are found in numerous plant species within the Leguminosae family; however, soy isoflavones particularly significant practice and have been extensively studied recent years. The health-promoting potential of orally administered is widely documented scientific literature, many review articles developed to highlight their significance. However, it should be noted that soy-isoflavone-rich extracts isolated isoflavones, such as genistein daidzein, also often applied topically ingredients formulations, including face creams, tonics, emulsions. New delivery systems continuously being enhance skin permeability thus improving efficacy. In this context, direct activity on cells an important aspect research. anti-inflammatory, protective, antioxidant properties make them promising cosmetic with anti-aging because inflammation accumulation reactive oxygen (ROS) can lead structural functional changes cells, accelerating aging process. This provides overview research impact application isoflavone extract soy-derived a focus molecular mechanisms underlying effects. study aims offer essential insights aid development cosmetics future clinical applications.

Language: Английский

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MiRNA Expression in Long-Distance Runners with Musculoskeletal Pain: Implications for Pain Pathophysiology

Biomedicines, Journal Year: 2024, Volume and Issue: 12(11), P. 2494 - 2494

Published: Oct. 30, 2024

: miRNAs are short, non-coding RNAs whose deregulation has been shown in painful processes, including musculoskeletal pain. This condition, which causes disability, impacts quality of life, and contributes to substantial healthcare costs, is also a critical issue sports. In this case-control study, we evaluated the expression four involved inflammation runners with pain elucidated their functions pathophysiological implications.

Language: Английский

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