Role of Oxidative Stress in Blood–Brain Barrier Disruption and Neurodegenerative Diseases

Antioxidants, Год журнала: 2024, Номер 13(12), С. 1462 - 1462

Опубликована: Ноя. 28, 2024

Upregulation of reactive oxygen species (ROS) levels is a principal feature observed in the brains neurodegenerative diseases such as Parkinson’s disease (PD) and Alzheimer’s (AD). In these diseases, oxidative stress can disrupt blood–brain barrier (BBB). This disruption allows neurotoxic plasma components, blood cells, pathogens to enter brain, leading increased ROS production, mitochondrial dysfunction, inflammation. Collectively, factors result protein modification, lipid peroxidation, DNA damage, and, ultimately, neural cell damage. this review article, we present mechanisms by which damage leads BBB breakdown brain diseases. Additionally, summarize potential therapeutic approaches aimed at reducing that contributes

Язык: Английский

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Meat products in human nutrition and health – About hazards and risks

Meat Science, Год журнала: 2024, Номер 218, С. 109628 - 109628

Опубликована: Авг. 24, 2024

Язык: Английский

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Methylglyoxal Formation—Metabolic Routes and Consequences

Antioxidants, Год журнала: 2025, Номер 14(2), С. 212 - 212

Опубликована: Фев. 13, 2025

Methylglyoxal (MGO), a by-product of glycolysis, plays significant role in cellular metabolism, particularly under stress conditions. However, MGO is potent glycotoxin, and its accumulation has been linked to the development several pathological conditions due oxidative stress, including diabetes mellitus neurodegenerative diseases. This paper focuses on biochemical mechanisms by which contributes through formation advanced glycation end products (AGEs), interactions with antioxidant systems, involvement chronic diseases like diabetes, neurodegeneration, cardiovascular disorders. exerts effects multiple signaling pathways, NF-κB, MAPK, Nrf2, induce stress. Additionally, triggers apoptosis primarily via intrinsic extrinsic while endoplasmic reticulum (ER) mediated PERK-eIF2α IRE1-JNK signaling. Moreover, activation inflammatory RAGE crucial pathogenesis these study points out connection between carbonyl increased formation, it should be an incentive search for marker that could have prognostic significance or targeted therapeutic intervention various

Язык: Английский

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Neuroprotective effects of dipeptidyl peptidase 4 inhibitor on Alzheimer’s disease: a narrative review

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Фев. 9, 2024

Insulin resistance in brain and amyloidogenesis are principal pathological features of diabetes-related cognitive decline development Alzheimer’s disease (AD). A growing body evidence suggests that maintaining glucose under control diabetic patients is beneficial for preventing AD development. Dipeptidyl peptidase 4 inhibitors (DDP4is) a class novel glucose-lowering medications through increasing insulin excretion decreasing glucagon levels have shown neuroprotective potential recent studies. This review consolidates extant from earlier new studies investigating the association between DPP4i use, AD, other outcomes. Beyond DPP4i’s benefits alleviating glucose-lowering, underlying mechanisms neuroprotection with were categorized into following sections: (Ferrari et al., Physiol Rev, 2021, 101, 1,047–1,081): DPP4is on directly ameliorating burden β-amyloid plaques reducing formation neurofibrillary tangles; bioactivity DPP4 substrates including glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), stromal-derived factor-1α (SDF-1α) etc.; pleiotropic effects neuronal cells intracerebral structure anti-inflammation, anti-oxidation, anti-apoptosis. We further revisited recently published epidemiological provided supportive data to compliment preclinical evidence. Given there remains lack completed randomized trials aim at assessing effect progression, this expected provide useful insight inhibition as therapeutic target prevention treatment. The helpful informing rationales future clinical research guiding evidence-based practice.

Язык: Английский

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Glucose addition and oven-heating of pork stimulate glycoxidation and protein carbonylation, while reducing lipid oxidation during simulated gastrointestinal digestion

Food Chemistry, Год журнала: 2024, Номер 453, С. 139662 - 139662

Опубликована: Май 16, 2024

Язык: Английский

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Proximal cysteine residues in proteins promote N-carboxyalkylation of lysine residues by α-dicarbonyl compounds

Journal of Biological Chemistry, Год журнала: 2025, Номер unknown, С. 108377 - 108377

Опубликована: Март 1, 2025

Advanced glycation end products (AGEs) are protein modifications resulting from the chemical reaction between lysine and arginine residues in proteins, carbonyl compounds, including glyoxal (GO) methylglyoxal (MGO). Nε-carboxymethyllysine (CML) Nε-carboxyethyllysine (CEL), formed by GO MGO, among major AGEs tissue proteins. Incubation with or MGO resulted higher CML CEL formation two cysteine containing αA-crystallin (αAC) than lacking αB-crystallin (αBC). Mass spectrometric data showed K70 K166 to be heavily modified αAC. In silico analysis of structure αAC proximal C142. Mutation reductive alkylation significantly reduced formation. The addition GSH N-acetylcysteine enhanced αBC. introduction a residue αBC increased accumulation. Our also that occurs through hemithioacetal intermediate thiols MGO. Together, these results highlight novel mechanism which influence AGE levels. Additionally, ligands for RAGE, receptor AGEs, has been implicated several aging diabetes-associated diseases. Therefore, further understanding biosynthesis could lead development new therapies against those

Язык: Английский

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Depletion of MGO or Its Derivatives Ameliorate CUMS-Induced Neuroinflammation

Cells, Год журнала: 2025, Номер 14(6), С. 397 - 397

Опубликована: Март 8, 2025

Advanced glycation end products (AGEs) are a series of structurally complex and harmful compounds formed through the reaction between carbonyl group reducing sugars (such as glucose fructose) free amino groups proteins, lipids, or nucleic acids. Excessive accumulation AGEs in body can trigger oxidative stress, induce inflammatory responses, contribute to development diabetes, atherosclerosis, neurological disorders. Within category dicarbonyl compounds, methylglyoxal (MGO)—a byproduct resulting from degradation—serves pivotal precursor formation induction neurotoxicity. Specifically, generated MGO display significant cytotoxicity toward cells central nervous system. Therefore, we aimed investigate role MGO-AGEs neuroinflammation mediated by CUMS. Interestingly, found that overexpression glyoxalase 1 (GLO1) reduced levels corticosterone-treated microglia, thereby alleviating response. Furthermore, GLO1 hippocampus chronically stressed mice levels, mitigating CUMS-induced cognitive impairment. Additionally, when using receptor for advanced (RAGE) inhibitor FPS-ZM1 primary microglia cells, observed despite corticosterone-induced elevation MGO, no response occurred. This suggests RAGE clearance reduce MGO-AGE-mediated Subsequently, used treat it significantly ameliorated dysfunction. These results suggest targeting metabolism could serve therapeutic approach manage stress-related mental

Язык: Английский

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Formation of Hesperetin-Methylglyoxal Adducts in Food and In Vivo, and Their Metabolism In Vivo and Potential Health Impacts

Journal of Agricultural and Food Chemistry, Год журнала: 2024, Номер 72(19), С. 11174 - 11184

Опубликована: Апрель 30, 2024

Polyphenols with a typical meta-phenol structure have been intensively investigated for scavenging of methylglyoxal (MGO) to reduce harmful substances in food. However, less attention has paid the formation level polyphenol-MGO adducts foods and vivo their absorption, metabolism, health impacts. In this study, hesperitin (HPT) was found scavenge MGO by forming two adducts, namely, 8-(1-hydroxyacetone)-hesperetin (HPT-mono-MGO) 6-(1-hydroxyacetone)-8-(1-hydroxyacetone)-hesperetin (HPT-di-MGO). These were detected (1.6–15.9 mg/kg total) cookies incorporated 0.01%–0.5% HPT. HPT-di-MGO main adduct rat plasma after HPT consumption. The absorbed 8–30 times faster than HPT, they underwent glucuronidation sulfation vivo. HPT-mono-MGO would continue react endogenous produce HPT-di-MGO, which effectively reduced cytotoxicity HPT-mono-MGO. This study provided data on safety employing as dietary supplement foods.

Язык: Английский

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Identification, Occurrence, and Mechanism of Formation of 1-Acetyl-β-carbolines Derived from l-Tryptophan and Methylglyoxal

Journal of Agricultural and Food Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 23, 2025

β-Carbolines (βCs) are bioactive compounds present in foods and biological systems. This work describes the identification, occurrence, mechanism of formation 1-acetyl-β-carbolines (1-acetyl-βCs) that result from reaction l-tryptophan with α-dicarbonyl compound methylglyoxal. Two β-carbolines characterized as 1-acetyl-β-carboline (AβC) 1-acetyl-β-carboline-3-carboxylic acid (AβC-COOH). Their was favored acidic conditions increasing temperature, but 1-acetyl-βCs also formed moderate temperatures a wide range pH, including physiological conditions, human serum. The relies on tautomerism cyclization to give 1-(1-hydroxyethyl)-3,4-dihydro-β-carboline-3-carboxylic intermediates followed by oxidation C1'-OH aromatization 1-acetyl-βCs. took place reactions fructose or glucose tryptophan under heating depended methylglyoxal released during carbohydrate degradation. Formation carbohydrates increased at neutral basic pH values more those conditions. Thus, could be advanced glycation end-products (AGEs). 1-Acetyl-βCs were identified quantified for first time many foods. AβC ranged undetectable 250 ng/g highest amount detected honey, bread, cookies, soy sauce, coffee. On average, AβC-COOH generally appeared lower concentrations than it 323 levels found fried bread. These results indicate relevant βCs vivo.

Язык: Английский

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Role of cystathionine-β-synthase and hydrogen sulfide in down syndrome

Neurotherapeutics, Год журнала: 2025, Номер unknown, С. e00584 - e00584

Опубликована: Апрель 1, 2025

Язык: Английский

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