Brain Transcriptome Changes Associated With an Acute Increase of Protein O‐GlcNAcylation and Implications for Neurodegenerative Disease

Journal of Neurochemistry, Год журнала: 2025, Номер 169(1)

Опубликована: Янв. 1, 2025

ABSTRACT Enhancing protein O‐GlcNAcylation by pharmacological inhibition of the enzyme O‐GlcNAcase (OGA) has been considered as a strategy to decrease tau and amyloid‐beta phosphorylation, aggregation, pathology in Alzheimer's disease (AD). There is still more be learned about impact enhancing global O‐GlcNAcylation, which important for understanding potential using OGA treat neurodegenerative diseases. In this study, we investigated acute effect pharmacologically increasing O‐GlcNAc levels, inhibitor Thiamet G (TG), normal mouse brains. We hypothesized that transcriptome signature response 3 h TG treatment (50 mg/kg) provides comprehensive view inhibition. then performed mRNA sequencing brain NovaSeq PE 150 ( n = 5 each group). identified 1234 significant differentially expressed genes with versus saline treatment. Functional enrichment analysis upregulated several pathways, including normally down AD. Among downregulated pathways were cell adhesion pathway well up AD aging. When comparing chronic treatment, autophosphorylation kinase activity upregulated, whereas astrocyte markers both datasets. AMPK subunit Prkab2 was one gene pathway, increase after confirmed qPCR. Interestingly, mitochondrial Data from will enable evaluation mechanisms underlying particular, inhibitors appear have downstream effects related bioenergetics may limit their therapeutic benefits. image

Язык: Английский

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Dietary Phytochemicals in Health and Disease: Mechanisms, Clinical Evidence, and Applications—A Comprehensive Review

Food Science & Nutrition, Год журнала: 2025, Номер 13(3)

Опубликована: Март 1, 2025

ABSTRACT Phytochemicals are bioactive compounds found in plants that play a key role promoting health and preventing diseases. Present fruits, vegetables, grains, seed oils, these considered safe for consumption due to the co‐evolution adaptation between mammals plants. Due their wide‐ranging biological effects, they have attracted considerable research interest. This comprehensive review explores mechanisms of action, benefits, applications dietary phytochemicals, with particular focus on groups such as polyphenols, flavonoids, carotenoids. Research shows phytochemicals interact nuclear membrane receptors, influence metabolic pathways, affect epigenetic modifications. Our highlights broad range activities compounds, including antioxidant, antibacterial, anti‐inflammatory, anti‐diabetic, anticancer all which contribute health‐promoting properties. Clinical evidence supports prevention management diseases cardiovascular disorders, conditions, cancer, diets rich being linked lower risk disease. also at cutting edge food preservation, supplements, emerging medical treatments. Additionally, we identified advancements extraction identification techniques, particularly metabolomics, further enhance areas. Despite promising challenges bioavailability, regulatory barriers, need robust clinical trials persist. However, innovative delivery systems like nanoparticles, liposomes, encapsulation offer potential solutions bioavailability by improving absorption stability. The concludes emphasizing personalized nutrition combination therapies benefits while stressing methods, trials, bioavailability.

Язык: Английский

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Norboldine improves cognitive impairment and pathological features in Alzheimer's disease by activating AMPK/GSK3β/Nrf2 signaling pathway

Journal of Ethnopharmacology, Год журнала: 2024, Номер 333, С. 118498 - 118498

Опубликована: Июнь 28, 2024

Язык: Английский

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Revealing rutaecarpine’s promise: A pathway to parkinson’s disease relief through PPAR modulation

International Immunopharmacology, Год журнала: 2025, Номер 147, С. 114076 - 114076

Опубликована: Янв. 13, 2025

Язык: Английский

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Resveratrol-Enhanced Human Neural Stem Cell-Derived Exosomes Mitigate MPP+-Induced Neurotoxicity Through Activation of AMPK and Nrf2 Pathways and Inhibition of the NLRP3 Inflammasome in SH-SY5Y Cells

Life, Год журнала: 2025, Номер 15(2), С. 294 - 294

Опубликована: Фев. 13, 2025

Parkinson's disease (PD) is a progressive neurodegenerative disorder primarily characterized by the loss of dopaminergic neurons in substantia nigra. Mitochondrial dysfunction, oxidative stress, and neuroinflammation are recognized as critical pathological mechanisms driving neurodegeneration PD. Exosome (Exo)-based therapies, particularly those derived from human neural stem cells (hNSCs), offer promising neuroprotective effects due to their ability transfer bioactive molecules that modulate cellular processes. Resveratrol (RES), polyphenolic compound with potent antioxidant anti-inflammatory properties, has been shown enhance therapeutic potential cell (SC)-derived Exos. This study investigated RES-treated hNSCs-derived Exos (RES-hNSCs-Exos) on SH-SY5Y exposed 1-methyl-4-phenylpyridinium (MPP+), neurotoxin commonly used model Parkinsonian neurotoxicity. Treating MPP+ led significant reductions viability, mitochondrial increased activation inflammatory pathways. Treatment RES-hNSCs-Exos rescued MPP+-induced toxicity improving enhancing ATP production, increasing biogenesis, reducing reactive oxygen species (ROS) generation. The findings also demonstrated expression essential genes involved such PGC1α, NRF1, Tfam, indicating improved function presence RES-hNSCs-Exos. Further analysis revealed these protective were mediated activating AMP-activated protein kinase (AMPK) Nrf2 signaling pathways, which promoted health reduced stress. Moreover, treatment suppressed downregulating NLRP3 inflammasome secretion pro-inflammatory cytokines IL-1β IL-18. In conclusion, results suggest exhibit against neurotoxicity function, inhibiting neuroinflammation. These highlight hNSCs-Exos novel strategy for diseases like PD, RES valuable enhancer efficacy.

Язык: Английский

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

Molecular Neurodegeneration, Год журнала: 2025, Номер 20(1)

Опубликована: Март 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.

Язык: Английский

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Identification and Exploration of Immunity‐Related Genes and Natural Products for Alzheimer's Disease Based on Bioinformatics, Molecular Docking, and Molecular Dynamics

Immunity Inflammation and Disease, Год журнала: 2025, Номер 13(4)

Опубликована: Апрель 1, 2025

ABSTRACT Background Recent research highlights the immune system's role in AD pathogenesis and promising prospects of natural compounds treatment. This study explores immunity‐related biomarkers potential products using bioinformatics, machine learning, molecular docking, kinetic simulation. Methods Differentially expressed genes (DEGs) were analyzed GSE5281 GSE132903 datasets. Important module identified a weighted co‐expression algorithm (WGCNA), immune‐related (IRGs) obtained from ImmPortPortal database. Intersecting these yielded important IRGs. Then, least absolute shrinkage selection operator (LASSO) other methods screened common markers. Biological pathways explored through Gene Ontology (GO), Kyoto Encyclopedia Genes Genomes (KEGG), Set Enrichment Analysis (GSEA). The accuracy markers was assessed by subject signature (ROC) curves validated GSE122063 dataset. datasets then subjected to immunoinfiltration analysis. Multiple compound databases used analyze core Chinese medicines components. Molecular docking simulation verification for further verification. Results A total 1360 differential 5 (PGF, GFAP, GPI, SST, NFKBIA) identified, showing excellent diagnostic efficiency. GSEA revealed associated with Oxidative phosphorylation, Nicotine addiction, Hippo signaling pathway. Immune infiltration analysis showed dysregulation multiple cell types brains, significant interactions between types. 27 possible herbs 7 eventually identified. binding environment GPI‐luteolin GPI‐stigasterol relatively stable good affinity. Conclusions PGF, NFKBIA early diagnosis, cells brains. compounds, including luteolin stigmasterol, targeting biomarkers.

Язык: Английский

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Phyto-nanotechnology: A novel beneficial strategy for Alzheimer's disease therapy

Neurochemistry International, Год журнала: 2024, Номер 180, С. 105868 - 105868

Опубликована: Сен. 25, 2024

Язык: Английский

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Novel Compounds as NLRP3 Inhibitors for Treating Alzheimer’s Disease and Parkinson’s Disease

ACS Medicinal Chemistry Letters, Год журнала: 2024, Номер 15(8), С. 1203 - 1204

Опубликована: Июль 29, 2024

Provided herein are novel compounds as NLRP3 inhibitors, pharmaceutical compositions, use of such in treating Alzheimer's disease and Parkinson's disease, processes for preparing compounds.

Язык: Английский

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Neuroprotective effects of Elaeagnus glabra f. oxyphylla extract in amyloid-beta-induced cognitive deficit mice: Involvement of the PKC-delta, MYL2, and FER pathways

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 181, С. 117671 - 117671

Опубликована: Ноя. 12, 2024

Язык: Английский

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