Metallothionein: A Comprehensive Review of Its Classification, Structure, Biological Functions, and Applications

Antioxidants, Journal Year: 2024, Volume and Issue: 13(7), P. 825 - 825

Published: July 9, 2024

Metallothionein is a cysteine-rich protein with high metal content that widely found in nature. In addition to heavy detoxification, metallothionein well known as potent antioxidant. The sulfhydryl of confers excellent antioxidant activity, enabling it effectively scavenge free radicals and mitigate oxidative stress damage. addition, can play neuroprotective role by alleviating damage nerve cells, have an anticancer effect enhancing the ability normal cells resist unfavorable conditions through its function, reduce inflammation scavenging reactive oxygen species. Due diverse biological functions, has broad potential for application environmental pollution, predicting diagnosing diseases, developing skin care products health foods. This review summarizes recent advances classification, structure, applications metallothionein, focusing on powerful effects related functions.

Language: Английский

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Neurotoxicity of manganese via ferroptosis induced by redox imbalance and iron overload

Ecotoxicology and Environmental Safety, Journal Year: 2024, Volume and Issue: 278, P. 116404 - 116404

Published: May 4, 2024

Manganese (Mn) is an essential trace element for maintaining bodily functions. Excessive exposure to Mn can pose serious health risks humans and animals, particularly the nervous system. While has been implicated as a neurotoxin, exact mechanism of its toxicity remains unclear. Ferroptosis form programmed cell death that results from iron-dependent lipid peroxidation. It plays role in various physiological pathological cellular processes may be closely related Mn-induced neurotoxicity. However, ferroptosis neurotoxicity not thoroughly investigated. Therefore, this study aims investigate Using bioinformatics, we identified significant changes genes associated with Mn-exposed animal models. We then evaluated at both levels. Our findings suggest causes weight loss system damage mice. In vitro vivo experiments have shown increases malondialdehyde, reactive oxygen species, ferrous iron, while decreasing glutathione adenosine triphosphate. These leads increase peroxidation disrupts iron metabolism, resulting oxidative stress injury ferroptosis. Furthermore, assessed expression levels proteins mRNAs ferroptosis, confirming involvement

Language: Английский

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Harnessing Ferroptosis to Overcome Drug Resistance in Colorectal Cancer: Promising Therapeutic Approaches

Cancers, Journal Year: 2023, Volume and Issue: 15(21), P. 5209 - 5209

Published: Oct. 30, 2023

Drug resistance remains a significant challenge in the treatment of colorectal cancer (CRC). In recent years, emerging field ferroptosis, unique form regulated cell death characterized by iron-dependent lipid peroxidation, has offered new insights and potential therapeutic strategies for overcoming drug CRC. This review examines role ferroptosis CRC its impact on resistance. It highlights distinctive features advantages compared to other pathways, such as apoptosis necrosis. Furthermore, discusses current research advances field, including novel approaches that target ferroptosis. These involve use inducers, interventions iron metabolism combination therapies enhance efficacy The also explores immunotherapy modulating strategy. Additionally, it evaluates strengths limitations targeting selectivity, low side effects, overcome resistance, well challenges related specificity development. Looking future, this prospects ferroptosis-based CRC, emphasizing importance further elucidate interaction between proposes future directions more effective strategies, development approaches, therapies, integration with fields precision medicine. conclusion, harnessing represents promising avenue Continued efforts are crucial optimizing outcomes providing hope patients.

Language: Английский

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Metallothionein II treatment mitigates rotenone-induced neurodegeneration in zebrafish models of Parkinson’s disease

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 31, 2025

Parkinson's disease (PD) is a common neurodegenerative disorder primarily affecting motor function due to progressive loss of dopaminergic neurons in the substantia nigra. Current therapies offer symptomatic relief but fail halt progression, highlighting need for novel therapeutic strategies. This study explores neuroprotective potential exogenous human metallothionein 2 (hMT2) peptide rotenone-induced PD zebrafish model. Adult were divided into four groups: control, rotenone-treated, hMT2 pre-treatment, and co-treatment. model was established by exposing 5 µg/L rotenone water 28 days. (0.2 µg) administered intracranially either one day before or seven days after exposure. The tank test demonstrated that exposure significantly impaired locomotor activity (p < 0.05) increased anxiety-like behavior 0.001). Additionally, exhibited reduced dopamine levels, decreased neuron population, elevated oxidative stress, heightened inflammatory response mitochondrial dysfunction. Treatment with hMT2, especially co-treatment group, ameliorated these deficits restoring activity, counts while reducing stress inflammation, improving function. These results suggest effect zebrafish. findings support MT as agent PD.

Language: Английский

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Inhibition of Protein Aggregation and Endoplasmic Reticulum Stress as a Targeted Therapy for α-Synucleinopathy

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(8), P. 2051 - 2051

Published: July 30, 2023

α-synuclein (α-syn) is an intrinsically disordered protein abundant in the central nervous system. Physiologically, regulates vesicle trafficking and neurotransmitter release presynaptic terminals. Pathologies related to misfolding aggregation of α-syn are referred as α-synucleinopathies, they constitute a frequent cause neurodegeneration. The most common α-synucleinopathy, Parkinson’s disease (PD), caused by abnormal accumulation dopaminergic neurons midbrain. This results overload, activation endoplasmic reticulum (ER) stress, and, ultimately, neural cell apoptosis To date, available treatment options for PD only symptomatic rely on dopamine replacement therapy or palliative surgery. As prevalence has skyrocketed recent years, there pending issue development new disease-modifying strategies. These include anti-aggregative agents that target directly (gene therapy, small molecules immunization), indirectly (modulators ER oxidative stress clearance pathways) combine both actions (natural compounds). Herein, we provide overview characteristic features structure pathogenic mechanisms could be targeted with novel molecular-based therapies.

Language: Английский

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Neuroprotective Strategies and Cell-Based Biomarkers for Manganese-Induced Toxicity in Human Neuroblastoma (SH-SY5Y) Cells

Biomolecules, Journal Year: 2024, Volume and Issue: 14(6), P. 647 - 647

Published: May 31, 2024

Manganese (Mn) is an essential heavy metal in the human body, while excess Mn leads to neurotoxicity, as observed this study, where 100 µM of was administered neuroblastoma (SH-SY5Y) cell model dopaminergic neurons neurodegenerative diseases. We quantitated pathway and gene changes homeostatic cell-based adaptations exposure. Utilizing Gene Expression Omnibus, we accessed GSE70845 dataset a microarray SH-SY5Y cells published by Gandhi et al. (2018) applied statistical significance cutoffs at p < 0.05. report 74 10 with significance. ReactomeGSA analyses demonstrated upregulation histones (5 out induced genes) histone deacetylases neuroprotective response remodel/mitigate Mn-induced DNA/chromatin damage. Neurodegenerative-associated occurred. NF-κB signaled protective responses via Sirtuin-1 reduce neuroinflammation. Critically, activated three pathways implicating deficits purine metabolism. Therefore, validated that urate, antioxidant, mitigated Mn-losses viability cells. discuss hypoxia mimetic trans-activator HIF-1α, central vascular hypoxic mitochondrial dysfunction. 3-fold increase mRNA levels for antioxidant metallothionein-III, which 100-fold mimetics deferoxamine zinc.

Language: Английский

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Multi-tissue transcriptomic and serum metabolomic assessment reveals systemic implications of acute ozone-induced stress response in male Wistar Kyoto rats

Metabolomics, Journal Year: 2023, Volume and Issue: 19(9)

Published: Sept. 10, 2023

Language: Английский

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Metallothionein expression in the central nervous system in response to chronic heavy metal exposure: possible neuroprotective mechanism

Environmental Geochemistry and Health, Journal Year: 2023, Volume and Issue: 45(11), P. 8257 - 8269

Published: Aug. 14, 2023

Abstract It has been reported that volcanoes release several tonnes of mercury per year among other heavy metals through eruptions, fumaroles, or diffuse soil degassing. Since a high percentage the world's population lives in vicinity an active volcano, aim this study is to evaluate accumulation these central nervous system and presence cellular mechanisms metal detoxification such as metallothioneins. To carry out study, wild mice (Mus musculus) chronically exposed volcanic environment were captured Furnas village (Azores, Portugal) compared with those trapped reference area (Rabo de Peixe, Azores, Portugal). On one hand, load evaluated by analyzing brain cerebellum using ICP-MS analyzer on metallothionein 2A studied immunofluorescence assays. Our results show higher mercury, cadmium lead non-exposed individuals and, addition, immunoreactivity for different areas cerebrum indicating possible neuroprotection process.

Language: Английский

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Hypocortisolemic ASIA: a vaccine- and chronic infection-induced syndrome behind the origin of long COVID and myalgic encephalomyelitis

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: July 9, 2024

Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), long COVID (LC) and post-COVID-19 vaccine show similarities in their pathophysiology clinical manifestations. These disorders are related to viral adjuvant persistence, immunological alterations, autoimmune diseases hormonal imbalances. A developmental model is postulated that involves the interaction between immune hyperactivation, hypophysitis pituitary hypophysitis, depletion. This process might begin with a deficient CD4 T-cell response infections genetically predisposed individuals (HLA-DRB1), followed by an uncontrolled CD8 hyperactivation elevated antibody production, some of which may be directed against autoantigens, can trigger direct damage pituitary, resulting decreased production hormones, such as ACTH. As disease progresses, prolonged exposure antigens lead exhaustion system, exacerbating symptoms pathology. It suggested these could included autoimmune/adjuvant-induced inflammatory (ASIA) because similar manifestations possible relationship genetic factors, polymorphisms HLA-DRB1 gene. In addition, it proposed treatment antivirals, corticosteroids/ginseng, antioxidants, metabolic precursors improve modulating response, function, inflammation oxidative stress. Therefore, purpose this review suggest origin adenohypophysis improvement after corticosteroid replacement therapy.

Language: Английский

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Exploring genetic determinants of silver oxide nanoparticle-induced seed priming for drought tolerance in wheat

Genetic Resources and Crop Evolution, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 9, 2024

Language: Английский

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