NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases

Redox Biology, Год журнала: 2021, Номер 41, С. 101947 - 101947

Опубликована: Март 20, 2021

Oxidative stress has been implicated in the pathogenesis of Alzheimer's disease (AD). Mitochondrial dysfunction is linked to oxidative and reactive oxygen species (ROS) neurotoxicity during AD. Impaired mitochondrial metabolism associated with brain damage While role NADPH oxidase 4 (NOX4), a major source ROS, identified damage, mechanism by which NOX4 regulates ferroptosis astrocytes AD remains unclear. Here, we show that protein levels were significantly elevated impaired cerebral cortex from patients APP/PS1 double-transgenic mouse model The 4-hydroxynonenal (4-HNE) malondialdehyde (MDA), marker stress-induced lipid peroxidation, also We demonstrate over-expression increases impairment inhibition respiration ATP production via reduction five complexes ETC human astrocytes. Moreover, elevation induces ROS (mtROS) production, fragmentation, cellular antioxidant process Furthermore, increased ferroptosis-dependent cytotoxicity activation peroxidation These results suggest promotes

Язык: Английский

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Hormones and oxidative stress: an overview

Free Radical Research, Год журнала: 2019, Номер 54(1), С. 1 - 26

Опубликована: Дек. 22, 2019

In aerobes, oxygen is essential for maintenance of life. However, incomplete reduction leads to generation reactive species. These oxidants oxidise biological macromolecules present in their vicinity and thereby impair cellular functions causing oxidative stress (OS). Aerobes have evolved both enzymatic nonenzymatic antioxidant defences protect themselves from OS. Although hormones as means coordination involve regulation physiological activities tissues by regulating metabolism, any change normal titre pathophysiological states. While, such melatonin, insulin, oestrogen, progesterone display features, thyroid hormone, corticosteroids catecholamines elicit free radical OS, the role testosterone inducing OS debateable. This review an attempt understand impact cross talk between modulating defence system under various conditions.

Язык: Английский

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Nutrition Management in Older Adults with Diabetes: A Review on the Importance of Shifting Prevention Strategies from Metabolic Syndrome to Frailty

Nutrients, Год журнала: 2020, Номер 12(11), С. 3367 - 3367

Опубликована: Ноя. 1, 2020

The increasing prevalence of older adults with diabetes has become a major social burden. Diabetes, frailty, and cognitive dysfunction are closely related to the mechanisms aging. Insulin resistance, arteriosclerosis, chronic inflammation, oxidative stress, mitochondrial may be common shared by frailty impairment. Hyperglycemia, hypoglycemia, obesity, vascular factors, physical inactivity, malnutrition important risk factors for impairment in diabetes. impact nutrients on health outcomes varies age; thus, shifting diet therapy strategies from treatment obesity/metabolic syndrome prevention necessary patients who over 75 years age, have or sarcopenia, experience malnutrition. For optimal energy intake, sufficient protein vitamin healthy dietary patterns should recommended. after middle age include awareness proper glycemic control aimed at extending life expectancy nutrition, exercise, connectivity. Nutritional combination metabolic control, participation/support can extend maintain quality mellitus.

Язык: Английский

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The brain as an insulin-sensitive metabolic organ

Molecular Metabolism, Год журнала: 2021, Номер 52, С. 101234 - 101234

Опубликована: Апрель 16, 2021

The brain was once thought of as an insulin-insensitive organ. We now know that the insulin receptor is present throughout and serves important functions in whole-body metabolism function. Brain signaling involved not only homeostatic processes but also neuropathological such cognitive decline Alzheimer's disease.

Язык: Английский

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Cognitive impairment and type 2 diabetes mellitus: Focus of SGLT2 inhibitors treatment

Pharmacological Research, Год журнала: 2022, Номер 176, С. 106062 - 106062

Опубликована: Янв. 10, 2022

Gliflozins are a novel class of oral anti-diabetic drugs, acting as inhibitors sodium-glucose co-transporters (SGLTs) through the proximal convoluted tubules (PCT) and intestinal epithelium. The 2 (SGLT2) mainly expressed in S1 S2 segments tubule kidneys. Clinical guidelines recommend their use especially Type Diabetes mellitus (T2DM) patients with vascular complications and/or heart failure highlighting importance co-transporter (SGLT2i) pleiotropic effects. Interestingly, cognitive decline is widely recognized complication T2DM and, addition, to clarify its pathophysiology, there an urgent need understand how if diabetes therapies can control diabetes-related dysfunction. At time, although SGLT2 proteins present Central Nervous System (CNS), SGLT2i effects on impairments remain partly unknown. In pre-clinical studies, ameliorates dysfunction obese mice, reducing oxidative stress, neuroinflammation improving neuronal plasticity mitochondrial brain pathway. could bring back mTOR physiological state activation, stopping neurodegenerative diseases' onset or progression. Instead, clinical studies T2DM-related treated by much more limited. For these reasons, further needed better elucidate therapy affect decline. this scenario, review aims summarize knowledge role stimulate new trials.

Язык: Английский

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Targeting Metabolic Diseases: The Role of Nutraceuticals in Modulating Oxidative Stress and Inflammation

Nutrients, Год журнала: 2024, Номер 16(4), С. 507 - 507

Опубликована: Фев. 10, 2024

The escalating prevalence of metabolic and cardiometabolic disorders, often characterized by oxidative stress chronic inflammation, poses significant health challenges globally. As the traditional therapeutic approaches may sometimes fall short in managing these conditions, attention is growing toward nutraceuticals worldwide; with compounds being obtained from natural sources potential beneficial effects shown to potentially support and, some cases, replace pharmacological treatments, especially for individuals who do not qualify conventional treatments. This review delves into burgeoning field nutraceutical-based modulation as a promising strategy attenuating inflammation disorders. Drawing an extensive body research, showcases various nutraceutical agents, such polyphenols, omega-3 fatty acids, antioxidants, which exhibit antioxidative anti-inflammatory properties. All can be classified novel drugs that are capable regulating pathways mitigate oxidative-stress- inflammation-associated diseases. By exploring mechanisms through interact immune responses, this highlights their restore redox balance temper inflammation. Additionally, prospects interventions discussed, encompassing bioavailability enhancement, personalized treatment approaches, clinical translation. Through comprehensive analysis latest scientific reports, article underscores avenue fight complex landscape particularly accentuating impact on cardiovascular health.

Язык: Английский

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Antioxidant Barrier, Redox Status, and Oxidative Damage to Biomolecules in Patients with Colorectal Cancer. Can Malondialdehyde and Catalase Be Markers of Colorectal Cancer Advancement?

Biomolecules, Год журнала: 2019, Номер 9(10), С. 637 - 637

Опубликована: Окт. 22, 2019

This study is the first to assess diagnostic utility of redox biomarkers in patients with colorectal cancer (CRC). Antioxidant barrier (Cu,Zn-superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reductase (GR), uric acid (UA), reduced (GSH)), status (total antioxidant (TAC)/oxidant (TOS), ferric reducing ability (FRAP)), and oxidative damage products (advanced glycation end (AGE), advanced oxidation protein (AOPP), malondialdehyde (MDA)) were measured serum/plasma samples 50 CRC patients. The activity SOD was significantly higher whereas CAT, GPx GR considerably lower compared control group (p < 0.0001). Levels UA, TOS, OSI concentrations AGE, AOPP, MDA higher, levels GSH, TAC, FRAP healthy controls AUC for CAT respect presence lymph node metastasis 0.7450 = 0.0036), according depth tumour invasion 0.7457 0.0118). associated enzymatic/non-enzymatic imbalance as well increased proteins lipids. Redox can be potential indicators advancement.

Язык: Английский

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Salivary Antioxidant Barrier, Redox Status, and Oxidative Damage to Proteins and Lipids in Healthy Children, Adults, and the Elderly

Oxidative Medicine and Cellular Longevity, Год журнала: 2019, Номер 2019, С. 1 - 12

Опубликована: Дек. 5, 2019

Despite the proven role of oxidative stress in numerous systemic diseases and process aging, little is still known about salivary redox balance healthy children, adults, elderly. Our study was first to assess antioxidant barrier, status, damage nonstimulated (NWS) stimulated (SWS) saliva as well blood samples individuals at different ages. We divided 90 generally people into three equally numbered groups based on age: 2–14 (children adolescents), 25–45 (adults), 65–85 (elderly people). Antioxidant enzymes (salivary peroxidase (Px), glutathione (GPx), catalase (CAT), superoxide dismutase-1 (SOD)), nonenzymatic antioxidants (reduced (GSH) uric acid (UA)), status (total capacity (TAC), total oxidant (TOS), index (OSI)), products (advanced glycation end (AGE), advanced oxidation protein (AOPP), malondialdehyde (MDA)) were evaluated NWS SWS erythrocyte/plasma samples. demonstrated that defense most effective aged 25–45. In elderly, we observed a progressive decrease efficiency central systems (↓GPx, ↓SOD, ↓GSH, ↓TAC erythrocytes plasma vs. adults) (↓Px, ↓UA, (↓TAC adults). Both local less efficient children adolescents than group middle-aged people, which indicates age-related immaturity mechanisms. Oxidative proteins (↑AGE, ↑AOPP) lipids (↑MDA) significantly higher elderly comparison with adults children/adolescents. Of all biomarkers, only reflected their content plasma. The level biomarkers did not vary gender.

Язык: Английский

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Empagliflozin Improves Insulin Sensitivity of the Hypothalamus in Humans With Prediabetes: A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Trial

Diabetes Care, Год журнала: 2021, Номер 45(2), С. 398 - 406

Опубликована: Окт. 29, 2021

OBJECTIVE Insulin action in the human brain reduces food intake, improves whole-body insulin sensitivity, and modulates body fat mass its distribution. Obesity type 2 diabetes are often associated with resistance, resulting impaired brain-derived modulation of peripheral metabolism. So far, no pharmacological treatment for resistance has been established. Since sodium–glucose cotransporter (SGLT2) inhibitors lower glucose levels modulate energy metabolism, we hypothesized that SGLT2 inhibition may be a approach to reverse resistance. RESEARCH DESIGN AND METHODS In this randomized, double-blind, placebo-controlled clinical trial, 40 patients (mean ± SD; age 60 9 years; BMI 31.5 3.8 kg/m2) prediabetes were randomized receive 25 mg empagliflozin every day or placebo. Before after 8 weeks treatment, sensitivity was assessed by functional MRI combined intranasal administration brain. RESULTS We identified significant interaction between time hypothalamic response insulin. Post hoc analyses revealed only empagliflozin-treated experienced increased responsiveness. Hypothalamic significantly mediated empagliflozin-induced decrease fasting liver fat. CONCLUSIONS Our results corroborate hypothalamus humans prediabetes. Treatment able restore favorable could contribute beneficial effects inhibitors. findings position as first potential benefits adiposity

Язык: Английский

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Incretin and insulin signaling as novel therapeutic targets for Alzheimer’s and Parkinson’s disease

Molecular Psychiatry, Год журнала: 2022, Номер 28(1), С. 217 - 229

Опубликована: Окт. 18, 2022

Abstract Despite an ever-growing prevalence and increasing economic burden of Alzheimer’s disease (AD) Parkinson’s (PD), recent advances in drug development have only resulted minimally effective treatment. In AD, along with amyloid tau phosphorylation, there is associated increase inflammation/glial activation, a decrease synaptic function, astrocyte state insulin resistance. PD, α-synuclein accumulation, inflammation, dysfunction, dopaminergic neuronal loss, some data to suggest Therapeutic strategies for neurodegenerative disorders commonly targeted individual pathological processes. An treatment might require either utilization multiple drugs which target the processes underlie or use single agent could influence Insulin incretins are compounds effects on Preclinical studies demonstrated that GLP-1 receptor agonists reduce neuroinflammation, deposition, improve memory formation. Incretin mimetics may act through restoration signaling pathways, inducing further neuroprotective effects. Currently, phase 2 3 trials underway AD PD populations. Here, we provide comprehensive review therapeutic potential incretin PD.

Язык: Английский

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