SLC7A11 as a Gateway of Metabolic Perturbation and Ferroptosis Vulnerability in Cancer

Antioxidants, Journal Year: 2022, Volume and Issue: 11(12), P. 2444 - 2444

Published: Dec. 11, 2022

SLC7A11 is a cell transmembrane protein composing the light chain of system xc-, transporting extracellular cystine into cells for cysteine production and GSH biosynthesis. critical gateway redox homeostasis by maintaining cellular levels that counter oxidative stress suppress ferroptosis. overexpressed in various human cancers regulates tumor development, proliferation, metastasis, microenvironment, treatment resistance. Upregulation needed to adapt high microenvironments maintain homeostasis. High basal ROS dependences cancer render them vulnerable further stress. Therefore, cyst(e)ine depletion may be an effective new strategy treatment. However, effectiveness inhibitors or cyst(e)inase has been established many preclinical studies but not reached stage clinical trials patients. A better understanding functions regulating interacting with redox-active proteins their substrates could promising this review intends understand role antioxidant signaling, regulators bioavailability cancer, linking signaling metabolism targeting novel therapeutics.

Language: Английский

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Metabolic phenotyping reveals an emerging role of ammonia abnormality in Alzheimer’s disease

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 7, 2024

The metabolic implications in Alzheimer's disease (AD) remain poorly understood. Here, we conducted a metabolomics study on moderately aging Chinese Han cohort (n = 1397; mean age 66 years). Conjugated bile acids, branch-chain amino acids (BCAAs), and glutamate-related features exhibited strong correlations with cognitive impairment, clinical stage, brain amyloid-β deposition 421). These demonstrated synergistic performances across stages subpopulations enhanced the differentiation of AD beyond demographics Apolipoprotein E ε4 allele (APOE-ε4). We validated their eight data sets (total n 7685) obtained from Disease Neuroimaging Initiative (ADNI) Religious Orders Study Memory Aging Project (ROSMAP). Importantly, identified are linked to blood ammonia homeostasis. further confirmed elevated level through development 1060). Our findings highlight as emphasize metabolite-mediated disturbance its potential signature therapeutic target for AD.

Language: Английский

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Glutamate Neurotoxicity and Destruction of the Blood–Brain Barrier: Key Pathways for the Development of Neuropsychiatric Consequences of TBI and Their Potential Treatment Strategies

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(17), P. 9628 - 9628

Published: Aug. 25, 2022

Traumatic brain injury (TBI) is associated with significant cognitive and psychiatric conditions. Neuropsychiatric symptoms can persist for years following injury, causing major disruptions in patients’ lives. In this review, we examine the role of glutamate as an aftereffect TBI that contributes to development neuropsychiatric We hypothesize causes long-term blood–brain barrier (BBB) dysfunction lasting many even decades. propose BBB central factor modulates increased after ultimately leads neurodegenerative processes subsequent manifestation Here, have identified factors determine upper lower levels concentration TBI. Furthermore, consider treatments integrity, including repairing controlling excess glutamate, potential therapeutic modalities treatment acute chronic conditions symptoms. By specifically focusing on BBB, restoring integrity will alleviate neurotoxicity related neurological sequelae.

Language: Английский

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Effect and mechanism of acupuncture on Alzheimer’s disease: A review

Frontiers in Aging Neuroscience, Journal Year: 2023, Volume and Issue: 15

Published: March 3, 2023

With the development trend of an aging society, Alzheimer’s disease (AD) has become urgent problem in field medicine worldwide. Cognitive impairment AD patients leads to a decline ability perform daily living and abnormalities behavior personality, causing abnormal psychiatric symptoms, which seriously affect life patients. Currently, mainly drug therapy is used for clinic, but large proportion will experience efficacy not working, even some drugs bring severe sleep disorders. Acupuncture, with its unique concept treatment method, been validated through number experiments proved reliability acupuncture AD. Many advances have made study neurobiological mechanisms AD, further demonstrating good advantages This review first summarizes pathogenesis then illustrates research progress includes effect on changes biochemical indicators vivo specific mechanism action exert therapeutic effect. Changes relevant similarly validate effectiveness treatment. The clinical mechanistic studies are intensified fit need social development. It believed that achieve new achievements as progresses.

Language: Английский

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Lutein Decreases Inflammation and Oxidative Stress and Prevents Iron Accumulation and Lipid Peroxidation at Glutamate-Induced Neurotoxicity

Antioxidants, Journal Year: 2022, Volume and Issue: 11(11), P. 2269 - 2269

Published: Nov. 17, 2022

The xanthophyll carotenoid lutein has been widely used as supplementation due to its protective effects in light-induced oxidative stress. Its antioxidant and anti-inflammatory features suggest that it a neuroprotective role well. Glutamate is major excitatory neurotransmitter the central nervous system (CNS), which plays key regulating brain function. Excess accumulation of intracellular glutamate accelerates an increase concentration reactive oxygen species (ROS) neurons leading neurotoxicity. In this study, we focused on SH-SY5Y neuroblastoma cells identify possible alterations stress, inflammation, iron metabolism affect neurological function itself presence lutein. First, ROS measurements were performed, then catalase (CAT) Superoxide Dismutase (SOD) enzyme activity determined by assay kits. ELISA technique was detect proinflammatory TNFα, IL-6, IL-8 cytokine secretions. Alterations uptake, storage, release followed gene expression Western blotting. Total level detections performed ferrozine-based detection method, heme kit for measurements. toward lipid-peroxidation RT-PCR. Our results show changes ROS, activity, modulate accumulation, may initiate lipid peroxidation cells. Meanwhile, attenuates glutamate-induced metabolism, peroxidation. According our findings, could be beneficial, supportive treatment neurodegenerative disorders.

Language: Английский

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The Integrity of the Blood–Brain Barrier as a Critical Factor for Regulating Glutamate Levels in Traumatic Brain Injury

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(6), P. 5897 - 5897

Published: March 20, 2023

A healthy blood-brain barrier (BBB) shields the brain from high concentrations of blood glutamate, which can cause neurotoxicity and neurodegeneration. It is believed that traumatic injury (TBI) causes long-term BBB disruption, subsequently increasing glutamate in blood, addition to increased resulting neuronal injury. Here, we investigate relationship between levels context permeability. Rats exposed disruption through an osmotic model or TBI treated with intravenous saline were compared control rats intact saline. After administration, cerebrospinal fluid tissue analyzed. The results showed a strong correlation groups disruption. We conclude protects permeability vital component regulating brain. These findings bring new approach treating consequences other diseases where central mechanism their development.

Language: Английский

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The Relationship between Post-Traumatic Stress Disorder Due to Brain Injury and Glutamate Intake: A Systematic Review

Nutrients, Journal Year: 2024, Volume and Issue: 16(6), P. 901 - 901

Published: March 21, 2024

There is a growing body of evidence that suggests connection between traumatic brain injury (TBI) and subsequent post-traumatic stress disorder (PTSD). While the exact mechanism unknown, we hypothesize chronic glutamate neurotoxicity may play role. The consumption dietary modifiable factor influencing levels in blood and, therefore, brain. In this systematic review, explored relationship development post-TBI PTSD. Of 1748 articles identified, 44 met inclusion criteria for analysis review. We observed individuals from countries with diets traditionally high had greater odds developing PTSD after TBI (odds ratio = 15.2, 95% confidence interval 11.69 to 19.76, p < 0.01). These findings support hypothesis chronically elevated concentrations caused by intake invoke neurodegeneration processes could ultimately result Further studies will clarify whether lowering via diet would be an effective strategy preventing or treating

Language: Английский

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Therapeutic potential of gut microbiota modulation in epilepsy: A focus on short-chain fatty acids

Neurobiology of Disease, Journal Year: 2025, Volume and Issue: unknown, P. 106880 - 106880

Published: March 1, 2025

According to the criteria established by International League Against Epilepsy (ILAE), epilepsy is defined as a disorder characterized at least two unprovoked seizures occurring more than 24 h apart. Its pathogenesis closely related various physiological and pathological factors. Advances in high-throughput metagenomic sequencing have increasingly highlighted role of gut microbiota dysbiosis epilepsy. Short-chain fatty acids (SCFAs), major metabolites key regulators gut-brain axis, support homeostasis through multiple mechanisms. Recent studies indicated that SCFAs not only regulate maintaining intestinal barrier integrity modulating immune responses, but also affect structure function blood-brain (BBB) neuroinflammation. This review, based on current literatures, explores relationship between epilepsy, emphasizing how BBB. In-depth may reveal their therapeutic potential inform development microbiota-targeted treatments.

Language: Английский

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The role of the mTOR pathway in diabetic retinopathy

Frontiers in Medicine, Journal Year: 2022, Volume and Issue: 9

Published: Nov. 1, 2022

The retina, the part of eye, translates light signal into an electric current that can be sent to brain as visual information. To achieve this, retina requires fine-tuned vascularization for its energy supply. Diabetic retinopathy (DR) causes alterations in eye reduce oxygen supply with consequent retinal neurodegeneration. During DR, mammalian target rapamycin (mTOR) pathway seems coordinate neurodegeneration multiple anabolic and catabolic processes, such autophagy, oxidative stress, cell death, release pro-inflammatory cytokines, which are closely related chronic hyperglycemia. This review outlines normal anatomy how hyperglycemia involved underlying this disease through over activation or inhibition mTOR pathway.

Language: Английский

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The Role of Micronutrients in Neurological Disorders

Nutrients, Journal Year: 2023, Volume and Issue: 15(19), P. 4129 - 4129

Published: Sept. 25, 2023

Trace elements and vitamins, collectively known as micronutrients, are essential for basic metabolic reactions in the human body. Their deficiency or, on contrary, an increased amount can lead to serious disorders. Research recent years has shown that long-term abnormal levels of micronutrients may be involved etiopathogenesis some neurological diseases. Acute chronic alterations micronutrient cause other complications Our aim was summarize knowledge about relation selected diseases comment their importance possibilities therapeutic intervention clinical practice.

Language: Английский

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