Cellular Metabolism: A Fundamental Component of Degeneration in the Nervous System

Biomolecules, Год журнала: 2023, Номер 13(5), С. 816 - 816

Опубликована: Май 11, 2023

It is estimated that, at minimum, 500 million individuals suffer from cellular metabolic dysfunction, such as diabetes mellitus (DM), throughout the world. Even more concerning knowledge that disease intimately tied to neurodegenerative disorders, affecting both central and peripheral nervous systems well leading dementia, seventh cause of death. New innovative therapeutic strategies address metabolism, apoptosis, autophagy, pyroptosis, mechanistic target rapamycin (mTOR), AMP activated protein kinase (AMPK), growth factor signaling with erythropoietin (EPO), risk factors apolipoprotein E (APOE-ε4) gene coronavirus 2019 (COVID-19) can offer valuable insights for clinical care treatment disorders impacted by disease. Critical insight into modulation these complex pathways are required since mTOR pathways, AMPK activation, improve memory retention in Alzheimer's (AD) DM, promote healthy aging, facilitate clearance β-amyloid (Aß) tau brain, control inflammation, but also may lead cognitive loss long-COVID syndrome through mechanisms include oxidative stress, mitochondrial cytokine release, APOE-ε4 if autophagy other programmed cell death left unchecked.

Язык: Английский

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The impact of aging and oxidative stress in metabolic and nervous system disorders: programmed cell death and molecular signal transduction crosstalk

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Ноя. 8, 2023

Life expectancy is increasing throughout the world and coincides with a rise in non-communicable diseases (NCDs), especially for metabolic disease that includes diabetes mellitus (DM) neurodegenerative disorders. The debilitating effects of disorders influence entire body significantly affect nervous system impacting greater than one billion people disability peripheral as well cognitive loss, now seventh leading cause death worldwide. Metabolic disorders, such DM, neurologic remain significant challenge treatment care individuals since present therapies may limit symptoms but do not halt overall progression. These clinical challenges to address interplay between warrant innovative strategies can focus upon underlying mechanisms aging-related oxidative stress, cell senescence, death. Programmed pathways involve autophagy, apoptosis, ferroptosis, pyroptosis play critical role oversee processes include insulin resistance, β-cell function, mitochondrial integrity, reactive oxygen species release, inflammatory activation. silent mating type information regulation 2 homolog 1

Язык: Английский

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The Metabolic Basis for Nervous System Dysfunction in Alzheimer’s Disease, Parkinson’s Disease, and Huntington’s Disease

Current Neurovascular Research, Год журнала: 2023, Номер 20(3), С. 314 - 333

Опубликована: Июль 25, 2023

Disorders of metabolism affect multiple systems throughout the body but may have greatest impact on both central and peripheral nervous systems. Currently available treatments behavior changes for disorders that include diabetes mellitus (DM) system diseases are limited cannot reverse disease burden. Greater access to healthcare a longer lifespan led an increased prevalence metabolic neurodegenerative disorders. In light these challenges, innovative studies into underlying pathways offer new treatment perspectives Alzheimer's Disease, Parkinson's Huntington's Disease. Metabolic intimately tied can lead debilitating outcomes, such as multi-nervous disease, susceptibility viral pathogens, long-term cognitive disability. Novel strategies robustly address involve careful consideration cellular metabolism, programmed cell death pathways, mechanistic target rapamycin (mTOR) its associated mTOR Complex 1 (mTORC1), 2 (mTORC2), AMP-activated protein kinase (AMPK), growth factor signaling, risk factors apolipoprotein E (APOE-ε4) gene. Yet, complex necessitate comprehensive understanding achieve clinical outcomes susceptibility, onset, progression.

Язык: Английский

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Receptor-dependent effects of sphingosine-1-phosphate (S1P) in COVID-19: the black side of the moon

Molecular and Cellular Biochemistry, Год журнала: 2023, Номер 478(10), С. 2271 - 2279

Опубликована: Янв. 18, 2023

Язык: Английский

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Mixed storm in SARS‐CoV‐2 infection: A narrative review and new term in the Covid‐19 era

Immunity Inflammation and Disease, Год журнала: 2023, Номер 11(4)

Опубликована: Апрель 1, 2023

Coronavirus disease 2019 (Covid-19) is caused by a novel severe acute respiratory syndrome coronavirus virus type 2 (SARS-CoV-2) leading to the global pandemic worldwide. Systemic complications in Covid-19 are mainly related direct SARS-CoV-2 cytopathic effects, associated hyperinflammation, hypercytokinemia, and development of cytokine storm (CS). As well, developed due propagation oxidative thrombotic events which may progress state called (TS), respectively. In addition, inflammatory lipid storms also activation cells release bioactive lipids correspondingly. Therefore, present narrative review aimed elucidate interrelated relationship between different types mixed (MS). conclusion, infection induces various including CS, storm, TS storm. These not developing alone since there close them. MS seems be more appropriate than it develops intricate interface reactive oxygen species, proinflammatory cytokines, complement activation, coagulation disorders, activated signaling pathway.

Язык: Английский

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Cognitive Impairment in Multiple Sclerosis

Bioengineering, Год журнала: 2023, Номер 10(7), С. 871 - 871

Опубликована: Июль 23, 2023

Almost three million individuals suffer from multiple sclerosis (MS) throughout the world, a demyelinating disease in nervous system with increased prevalence over last five decades, and is now being recognized as one significant etiology of cognitive loss dementia. Presently, modifying therapies can limit rate relapse potentially reduce brain volume patients MS, but unfortunately cannot prevent progression or onset disability. Innovative strategies are therefore required to address areas inflammation, immune cell activation, survival that involve novel pathways programmed death, mammalian forkhead transcription factors (FoxOs), mechanistic target rapamycin (mTOR), AMP activated protein kinase (AMPK), silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), associated apolipoprotein E (APOE-ε4) gene severe acute respiratory syndrome coronavirus (SARS-CoV-2). These intertwined at levels metabolic oversight cellular metabolism dependent upon nicotinamide adenine dinucleotide (NAD+). Insight into mechanisms these provide new avenues discovery for therapeutic treatment dementia cognition occurs during MS.

Язык: Английский

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Unveiling citicoline's mechanisms and clinical relevance in the treatment of neuroinflammatory disorders

The FASEB Journal, Год журнала: 2024, Номер 38(17)

Опубликована: Сен. 1, 2024

Citicoline, a compound produced naturally in small amounts the human body, assumes pivotal role phosphatidylcholine synthesis, dynamic constituent of membranes neurons. Across diverse models brain injury and neurodegeneration, citicoline has demonstrated its potential through neuroprotective anti-inflammatory effects. This review aims to elucidate citicoline's mechanism clinical implications conditions such as ischemic stroke, head trauma, glaucoma, age-associated memory impairment. Citicoline's prowess is rooted ability stabilize cellular membranes, thereby curbing excessive release glutamate-a pro-inflammatory neurotransmitter. Moreover, it actively diminishes free radicals inflammatory cytokines productions, which could otherwise harm neurons incite neuroinflammation. It also exhibits modulate microglia activity, brain's resident immune cells, hinder activation NF-κB, transcription factor governing genes. Clinical trials have subjected rigorous scrutiny patients grappling with acute age-related While findings from these are mixed, numerous studies suggest that confer improvements neurological function, disability reduction, expedited recovery, cognitive decline prevention within cohorts. Additionally, boasts favorable safety profile high tolerability. In summary, stands promising agent, wielding both across spectrum conditions. However, further research imperative delineate optimal dosage, treatment duration, underlying mechanisms. identifying specific patient subgroups most likely reap benefits new therapy remains critical avenue for exploration.

Язык: Английский

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SARS-CoV-2 infection and dysregulation of nuclear factor erythroid-2-related factor 2 (Nrf2) pathway

Cell Stress and Chaperones, Год журнала: 2023, Номер 28(6), С. 657 - 673

Опубликована: Окт. 5, 2023

Coronavirus disease 2019 (COVID-19) is a recent pandemic caused by novel severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) leading to pulmonary and extra-pulmonary manifestations due the development of oxidative stress (OS) hyperinflammation. The underlying cause for OS hyperinflammation in COVID-19 may be related inhibition nuclear factor erythroid 2-related (Nrf2), master regulator antioxidative responses cellular homeostasis. Nrf2 pathway inhibits expression pro-inflammatory cytokines cytokine storm COVID-19. activators can attenuate endothelial dysfunction (ED), renin-angiotensin system (RAS) dysregulation, immune thrombosis, coagulopathy. Hence, this review aimed reveal potential role its management As well, we tried revise mechanistic

Язык: Английский

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Potential role of tirzepatide towards Covid-19 infection in diabetic patients: a perspective approach

Inflammopharmacology, Год журнала: 2023, Номер 31(4), С. 1683 - 1693

Опубликована: Май 19, 2023

Abstract In Covid-19, variations in fasting blood glucose are considered a distinct risk element for bad prognosis and outcome Covid-19 patients. Tirazepatide (TZT), dual glucagon-like peptide-1 (GLP-1)and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist may be effective managing Covid-19-induced hyperglycemia diabetic non-diabetic The beneficial effect of TZT T2DM obesity is related to direct activation GIP GLP-1 receptors with subsequent improvement insulin sensitivity reduction body weight. improves endothelial dysfunction (ED) associated inflammatory changes through modulation homeostasis, sensitivity, pro-inflammatory biomarkers release. TZT, the receptor, produce effects against severity since agonists (GLP-1RAs) have anti-inflammatory pulmoprotective implications Covid-19. Therefore, GLP-1RAs could effectively treat severely affected Notably, using patients prevents variability, common finding like therapeutic strategy prevent variability-induced complications. signaling pathways highly activated, resulting hyperinflammation. reduce IL-6, CRP, ferritin TZ by reducing burden. anti-obesogenic ameliorating weight adiposity. Furthermore, induce substantial alterations gut microbiota. GLP-1RA preserves microbiota intestinal dysbiosis. Herein, other GLP-1RA, attenuate and, this mechanism, mitigate inflammation systemic complications either or obesity. As opposed that, was reduced obese However, GIP-1R homeostasis. Thus, both GLP-1, obesity-mediated inflammation. response meal impaired, leading postprandial abnormal development variability hyperglycemia-induced oxidative stress. Moreover, exaggerated disorders due release cytokines IL-1β, TNF-α lead cytokine storm development. Besides, GIP-1 inhibits expression MCP-1, chemokines TNF-α. GIP-1RA inhibit onset conclusion, receptors, SARS-CoV-2-induced hyperinflammation

Язык: Английский

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Causal influences of osteoarthritis on COVID-19: a Mendelian randomization study

Frontiers in Medicine, Год журнала: 2023, Номер 10

Опубликована: Окт. 31, 2023

Although observational and genetic studies have indicated a correlation between OA COVID-19, it remains uncertain whether osteoarthritis (OA) contributes to the severity of COVID-19. Here, we aimed investigate potential causal links two.In this study, conducted Mendelian randomization (MR) analysis there is connection COVID-19 outcomes. The utilized publicly available GWAS summary datasets, incorporating data on (N = 455,221), SARS-CoV-2 infection 2,597,856), hospitalized 2,095,324), critical 1,086,211). Additionally, performed literature establish molecular network connecting COVID-19.The MR showed effects (OR: 1.21, 95% CI: 1.02-1.43, p 0.026) 1.35, 1.09-1.68, 0.006) but not as such 1.00, 0.92-1.08, 0.969). Moreover, literature-based pathway uncovered set specific genes, CALCA, ACE, SIRT1, TNF, IL6, CCL2, others, that were found mediate association COVID-19.Our findings indicate elevates risk severe Therefore, larger efforts should be made in prevention patients.

Язык: Английский

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