Insulin Resistance and Oxidative Stress in the Brain: What’s New?

International Journal of Molecular Sciences, Год журнала: 2019, Номер 20(4), С. 874 - 874

Опубликована: Фев. 18, 2019

The latest studies have indicated a strong relationship between systemic insulin resistance (IR) and higher incidence of neurodegeneration, dementia, mild cognitive impairment. Although some these abnormalities could be explained by chronic hyperglycaemia, hyperinsulinemia, dyslipidaemia, and/or prolonged whole-body inflammation, the key role is attributed to neuronal redox imbalance oxidative damage. In this mini review, we provide schematic overview intracellular stress mitochondrial in IR brain. We highlight important correlations found so far brain stress, ceramide generation, β-amyloid accumulation, as well apoptosis conditions.

Язык: Английский

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High-Throughput Screening Platforms in the Discovery of Novel Drugs for Neurodegenerative Diseases

Bioengineering, Год журнала: 2021, Номер 8(2), С. 30 - 30

Опубликована: Фев. 23, 2021

Neurodegenerative diseases (NDDs) are incurable and debilitating conditions that result in progressive degeneration and/or death of nerve cells the central nervous system (CNS). Identification viable therapeutic targets new treatments for CNS disorders particular, NDDs is a major challenge field drug discovery. These difficulties can be attributed to diversity involved, extreme complexity neural circuits, limited capacity tissue regeneration, our incomplete understanding underlying pathological processes. Drug discovery complex multidisciplinary process. The screening attrition rate current protocols mean only one may arise from millions screened compounds resulting need improve technologies address multiple causes attrition. This has identified screen larger libraries where use efficient high-throughput (HTS) becomes key HTS investigate hundreds thousands per day. However, if fewer could without compromising probability success, cost time would largely reduced. To end, recent advances computer-aided design, silico libraries, molecular docking software combined with upscaling cell-based platforms have evolved efficiency higher predictability clinical applicability. We review, here, increasing role contemporary processes, particular NDDs, evaluate criteria its successful application. also discuss requirement novel NDD therapies examine challenges validating developing NDDs.

Язык: Английский

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Salivary biomarkers: novel noninvasive tools to diagnose chronic inflammation

International Journal of Oral Science, Год журнала: 2023, Номер 15(1)

Опубликована: Июнь 29, 2023

Abstract Several chronic disorders including type 2 diabetes (T2D), obesity, heart disease and cancer are preceded by a state of low-grade inflammation. Biomarkers for the early assessment encompass acute phase proteins (APP), cytokines chemokines, pro-inflammatory enzymes, lipids oxidative stress mediators. These substances enter saliva through blood flow and, in some cases, there is close relation between their salivary serum concentration. Saliva can be easily collected stored with non-invasive cost-saving procedures, it emerging concept to use detection inflammatory biomarkers. To this purpose, present review aims discuss advantages challenges using standard cutting-edge techniques discover biomarkers which may used diagnosis/therapy several diseases consequences pursuit possibly replace conventional paths detectable soluble mediators saliva. Specifically, describes procedures collection, approaches measurement novel methodological strategies such as biosensors improve quality care chronically affected patients.

Язык: Английский

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Advances in Applying Computer-Aided Drug Design for Neurodegenerative Diseases

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(9), С. 4688 - 4688

Опубликована: Апрель 28, 2021

Neurodegenerative diseases (NDs) including Alzheimer’s disease, Parkinson’s amyotrophic lateral sclerosis, and Huntington’s disease are incurable affect millions of people worldwide. The development treatments for this unmet clinical need is a major global research challenge. Computer-aided drug design (CADD) methods minimize the huge number ligands that could be screened in biological assays, reducing cost, time, effort required to develop new drugs. In review, we provide an introduction CADD examine progress applying other molecular docking studies NDs. We updated overview potential therapeutic targets various NDs discuss some advantages disadvantages these tools.

Язык: Английский

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Employing nanoparticle tracking analysis of salivary neuronal exosomes for early detection of neurodegenerative diseases

Translational Neurodegeneration, Год журнала: 2023, Номер 12(1)

Опубликована: Фев. 7, 2023

Abstract Neurodegenerative diseases are a set of progressive and currently incurable that primarily caused by neuron degeneration. often lead to cognitive impairment dyskinesias. It is now well recognized molecular events precede the onset clinical symptoms years. Over past decade, intensive research attempts have been aimed at early diagnosis these diseases. Recently, exosomes shown play pivotal role in occurrence progression many including cancer neurodegenerative Additionally, because can cross blood–brain barrier, they may serve as diagnostic tool for neural dysfunction. In this review, we detail mechanisms current challenges diseases, briefly review propose novel strategy based on salivary neuronal nanoparticle tracking analysis could be employed screening

Язык: Английский

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A Case-Control Study of Salivary Redox Homeostasis in Hypertensive Children. Can Salivary Uric Acid be a Marker of Hypertension?

Journal of Clinical Medicine, Год журнала: 2020, Номер 9(3), С. 837 - 837

Опубликована: Март 19, 2020

Oxidative stress plays a critical role in the pathogenesis of hypertension; however, there are no data on salivary redox homeostasis and gland function children with hypertension. A total 53 hypertension age- sex-matched controls were classified for study. The antioxidant barrier oxidative/nitrosative evaluated non-stimulated (NWS) stimulated (SWS) whole saliva, plasma, erythrocytes, Student’s t-test Mann–Whitney U-test used statistical analysis. We demonstrated that activities superoxide dismutase, catalase, peroxidase significantly higher NWS, SWS, erythrocytes hypertension, similar to oxidative damage proteins (advanced glycation end products) lipids (malondialdehyde) as well nitrosative markers (peroxynitrite nitrotyrosine). level uric acid (UA) was plasma UA concentration SWS correlated positively systolic diastolic blood pressure content plasma. This parameter differentiates from healthy (AUC = 0.98) high degree sensitivity (94%) specificity (94%). Stimulated flow lower group, protein amylase activity. In summary, childhood is associated hyposalivation disturbances defense enhanced both plasma/erythrocytes saliva. Salivary may be potential biomarker children.

Язык: Английский

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The Role of the Thioredoxin System in Brain Diseases

Antioxidants, Год журнала: 2022, Номер 11(11), С. 2161 - 2161

Опубликована: Окт. 31, 2022

The thioredoxin system, consisting of (Trx), reductase (TrxR), and NADPH, plays a fundamental role in the control antioxidant defenses, cell proliferation, redox states, apoptosis. Aberrations Trx system may lead to increased oxidative stress toxicity neurodegenerative processes. This study reviews pathophysiology treatment Alzheimer’s, Parkinson’s Huntington’s diseases, brain stroke, multiple sclerosis. an important those disorders via interactions through stress, apoptotic, neuro-immune, pro-survival pathways. Multiple aberrations TrxR systems related other their reciprocal relationships with neurodegenerative, neuro-inflammatory, neuro-oxidative pathways are here analyzed. Genetic environmental factors (nutrition, metals, toxins) impact function thereby contributing neuropsychiatric disease. could be promising drug target prevent treat processes, disorders.

Язык: Английский

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Electrochemical Biosensor for Point-of-Care Testing of Low-Abundance Biomarkers of Neurological Diseases

Analytical Chemistry, Год журнала: 2024, Номер 96(25), С. 10332 - 10340

Опубликована: Июнь 12, 2024

The neurofilament protein light chain (NEFL) is a potential biomarker of neurodegenerative diseases, and interleukin-6 (IL-6) also closely related to neuroinflammation. Especially, NEFL IL-6 are the two most low-abundance known markers neurological making their detection very important for early diagnosis prognosis prediction such kinds diseases. Nevertheless, quantitative low concentrations in serum remains quite difficult, especially point-of-care test (POCT). Herein, we developed portable, sensitive electrochemical biosensor combined with smartphones that can be applied multiple scenarios IL-6, meeting need POCT. We used double-antibody sandwich configuration polyenzyme-catalyzed signal amplification improve sensitivity sera. could detect as 5.22 pg/mL 3.69 6 μL within 2 h, demonstrating this worked well systems. Results showed its superior capabilities over those high-sensitivity ELISA samples. Importantly, by detecting sera, POCT model all biomarkers it possible mass screening patients

Язык: Английский

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A Longitudinal Study of the Antioxidant Barrier and Oxidative Stress in Morbidly Obese Patients after Bariatric Surgery. Does the Metabolic Syndrome Affect the Redox Homeostasis of Obese People?

Journal of Clinical Medicine, Год журнала: 2020, Номер 9(4), С. 976 - 976

Опубликована: Апрель 1, 2020

This is the first study to evaluate both antioxidant barrier, glutathione metabolism, and oxidative damage proteins lipids in morbidly obese patients undergoing bariatric treatment. The included 65 with class 3 obesity divided into two subgroups: without metabolic syndrome (OB) (OB + MS). Blood samples were collected before surgery as well one, three, six, twelve months after Superoxide dismutase reduced (GSH) significantly decreased, whereas reductase uric acid enhanced compared lean control. Moreover, OB group, we observed increase of superoxide (SOD) decrease (UA) treatment; however, these changes not MS group. (advanced glycation end products, AGE; advanced oxidation protein AOPP) (8-isoprostanes, 8-isop; 4-hydroxynoneal) was higher patients. We noticed that AGE AOPP levels diminished treatment, redox status (ratio GSH oxidized glutathione) still Summarizing, morbid associated disturbances barrier lipids. Although improves homeostasis patients, those show a continuous status. In supplementation may be considered.

Язык: Английский

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Salivary Biomarkers of Oxidative Stress and Inflammation in Stroke Patients: From Basic Research to Clinical Practice

Oxidative Medicine and Cellular Longevity, Год журнала: 2021, Номер 2021(1)

Опубликована: Янв. 1, 2021

Cerebral stroke is a serious worldwide health problem, as can be seen by the global epidemic of disease. In this disorder, when blood flow compromised ruptures or blocked arteries, sudden death neurons observed result lack oxygen and nutrients. Numerous severe problems frequent complications also exist in patients; therefore, there an urgent need to develop new therapeutic, diagnostic, prognostic methods for At present, diagnosis based on neurological examination, medical history, neuroimaging, due fact that rapid noninvasive diagnostic tests are unavailable. Nevertheless, oxidative stress inflammation considered key factors pathogenesis. Oxygen free radicals responsible oxidation lipids, proteins, DNA/RNA, which turn contributes damage brain. Toxic products reactions act cytostatically cell damaging membranes leading neuronal apoptosis necrosis. Thus, it seems redox/inflammatory biomarkers might used Nowadays, saliva increasing interest clinical laboratory medicine. Redox could obtained easily, noninvasively, cheaply, stress‐free from saliva. This minireview aimed at presenting current knowledge concerning use salivary prognosis stroke.

Язык: Английский

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