The Role of Autophagy in Copper-Induced Apoptosis and Developmental Neurotoxicity in SH-SY5Y Cells

Toxics, Год журнала: 2025, Номер 13(1), С. 63 - 63

Опубликована: Янв. 17, 2025

Copper (Cu) is a global environmental pollutant that poses serious threat to humans and ecosystems. induces developmental neurotoxicity, but the underlying molecular mechanisms are unknown. Neurons nonrenewable, they unable mitigate excessive accumulation of pathological proteins organelles in cells, which can be ameliorated by autophagic degradation. In this study, we established an vitro model Cu2+-exposed (0, 15, 30, 60 120 μM) SH-SY5Y cells explore role autophagy copper-induced neurotoxicity. The results showed copper resulted reduction shortening neural synapses differentiated cultured downregulated Wnt signaling pathway, nuclear translocation β-catenin. Exposure Cu2+ increased autophagosome flux blockage terms sequestosome 1 (p62/SQSTM1) microtubule-associated protein light chain 3B (LC3B) II/LC3BI expressions inhibition phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR pathway. Furthermore, induced apoptosis, characterized Bcl2 X (Bax), caspase 3, Poly (ADP-ribose) polymerase (PARP) decreased expression B-cell lymphoma 2 (Bcl2). Compared with μM exposure group alone, activator rapamycin pretreatment β-catenin translocation, LC3BII/LC3BI p62, as well upregulated 3 PARP. contrast, after inhibitor chloroquine pretreatment, were decreased, levels p62 upregulated, was while Bax, PARP increased. conclusion, study demonstrated associated neurotoxicity via might deepen understanding mechanism exposure.

Язык: Английский

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Impact of cuproptosis in gliomas pathogenesis with targeting options

Chemico-Biological Interactions, Год журнала: 2025, Номер unknown, С. 111394 - 111394

Опубликована: Янв. 1, 2025

Язык: Английский

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The Role of Ferroptosis and Cuproptosis in Tuberculosis Pathogenesis: Implications for Therapeutic Strategies

Current Issues in Molecular Biology, Год журнала: 2025, Номер 47(2), С. 99 - 99

Опубликована: Фев. 5, 2025

Tuberculosis (TB) caused by Mycobacterium tuberculosis (M.tb) remains a global health crisis, with over 10 million people affected annually. Despite advancements in treatment, M.tb has developed mechanisms to evade host immune responses, complicating efforts eradicate the disease. Two emerging cell death pathways, ferroptosis and cuproptosis, have been linked TB pathogenesis. Ferroptosis, an iron-dependent form of death, is driven lipid peroxidation reactive oxygen species (ROS) accumulation. This process can limit replication depleting intracellular iron inducing macrophage necrosis. However, excessive may lead tissue damage aid bacterial dissemination. Cuproptosis, triggered copper accumulation, disrupts mitochondrial metabolism, leading protein aggregation death. exploits both metabolism survive within macrophages, manipulating these processes resist oxidative stress responses. review examines roles cuproptosis TB, discussing how manipulates pathways for survival. While therapeutic strategies targeting processes, such as inducers (Erastin, RSL3) inhibitors (Ferrostatin-1) ionophores (Disulfiram, Elesclomol) chelators, show promise, limited understanding potential off-target effects significant challenge. Further exploration provide insights into development targeted therapies aimed at controlling infection while minimizing damage. By elucidating complex interactions between ferroptosis, future could better address resistance improve clinical outcomes.

Язык: Английский

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Genetic Damage and Multi-Elemental Exposure in Populations in Proximity to Artisanal and Small-Scale Gold (ASGM) Mining Areas in North Colombia

Toxics, Год журнала: 2025, Номер 13(3), С. 202 - 202

Опубликована: Март 11, 2025

This study evaluates DNA damage and multi-element exposure in populations from La Mojana, a region of North Colombia heavily impacted by artisanal small-scale gold mining (ASGM). markers the cytokinesis-block micronucleus cytome (CBMN-Cyt) assay, including micronucleated binucleated cells (MNBN), nuclear buds (NBUDs) nucleoplasmic bridges (NPB), were assessed 71 exposed individuals 37 unexposed participants. Exposed had significantly higher MNBN frequencies (PR = 1.26, 95% CI: 1.02–1.57, p 0.039). Principal Component Analysis (PCA) identified “Soil-Derived Mining-Associated Elements” (PC1), V, Fe, Al, Co, Ba, Se Mn, as being strongly associated with high population 10.45, 9.75–12.18, < 0.001). GAMLSS modeling revealed non-linear effects PC1, greater increases at concentrations, especially individuals. These results highlight dual role essential toxic elements, low concentrations potentially protective but increasing genotoxicity. Women consistently exhibited than men, suggesting sex-specific susceptibilities. highlights compounded risks chronic metal mining-impacted regions underscores urgent need for targeted interventions to mitigate genotoxic vulnerable populations.

Язык: Английский

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Mitochondrial dysfunction in AMI: mechanisms and therapeutic perspectives

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Апрель 10, 2025

Acute myocardial infarction (AMI) and the ischemia-reperfusion injury (MI/RI) that typically ensues represent a significant global health burden, accounting for considerable number of deaths disabilities. In context AMI, percutaneous coronary intervention (PCI) is preferred treatment option reducing acute ischemic damage to heart. Despite modernity PCI therapy, pathological cardiomyocytes due MI/RI remains an important target affects long-term prognosis patients. recent years, mitochondrial dysfunction during AMI has been increasingly recognized as critical factor in cardiomyocyte death. Damaged mitochondria play active role formation inflammatory environment by triggering key signaling pathways, including those mediated cyclic GMP-AMP synthase, NOD-like receptors Toll-like receptors. This review emphasizes dual both contributors regulators inflammation. The aim explore complex mechanisms its profound impact on immune dysregulation. Specific interventions mitochondrial-targeted antioxidants, membrane-stabilizing peptides, transplantation therapies have demonstrated efficacy preclinical models.

Язык: Английский

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Advancing Cancer Therapy with Nanomaterials Targeting Metalloptosis Mechanisms

IGI Global eBooks, Год журнала: 2025, Номер unknown, С. 503 - 530

Опубликована: Апрель 25, 2025

Despite the widespread use of traditional cancer therapies such as surgery, chemotherapy, and radiation, these approaches often suffer from significant drawbacks. Nanomaterials (NMs) are a promising alternative due to their distinct nanoscale properties which enable more precise drug delivery reduced off-target effects. Recently, cuproptosis ferroptosis have emerged novel forms programmed cell death regulated by metal ions, offering pathways for therapy. Cuproptosis, caused copper ion accumulation, leads mitochondrial dysfunction, while ferroptosis, driven iron-mediated lipid peroxidation, disrupts cellular integrity through oxidative stress. Here, we propose explore how NMs can be harnessed induce metalloptosis, advanced treatment strategies. Variations in NM size, morphology, synergistic effects composite complicate identification individual mechanisms. Use therapy, requires focusing on design regulation metalloptosis pathways.

Язык: Английский

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Mitochondrial pathways of copper neurotoxicity: focus on mitochondrial dynamics and mitophagy

Frontiers in Molecular Neuroscience, Год журнала: 2024, Номер 17

Опубликована: Дек. 5, 2024

Copper (Cu) is essential for brain development and function, yet its overload induces neuronal damage contributes to neurodegeneration other neurological disorders. Multiple studies demonstrated that Cu neurotoxicity associated with mitochondrial dysfunction, routinely assessed by reduction of membrane potential. Nonetheless, the role alterations dynamics in dysfunction induced exposure still debatable. Therefore, objective present narrative review was discuss Cu-induced special emphasis on influence fusion fission, as well clearance mitophagy. Existing data demonstrate that, addition electron transport chain inhibition, damage, reactive oxygen species (ROS) overproduction, overexposure inhibits down-regulation Opa1, Mfn1, Mfn2 expression, while promoting fission through up-regulation Drp1. It has been also PINK1/Parkin-dependent mitophagy cells, considered a compensatory response dysfunction. However, long-term high-dose impairs mitophagy, resulting accumulation dysfunctional mitochondria. inhibition biogenesis due PGC-1α further aggravates brain. Studies from non-brain cells corroborate these findings, offering additional evidence dysregulation may be involved Finally, cuproptosis proteotoxic stress, contribute pathogenesis certain diseases. Based it assumed mitoprotective agents, specifically targeting mechanisms quality control, would useful prevention neurotoxic effects overload.

Язык: Английский

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Decoding Osteoporosis: Understanding the Disease, Exploring Current and New Therapies and Emerging Targets.

Journal of Orthopaedic Reports, Год журнала: 2024, Номер unknown, С. 100472 - 100472

Опубликована: Сен. 1, 2024

Язык: Английский

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Tumor Biology Hides Novel Therapeutic Approaches to Diffuse Large B-Cell Lymphoma: A Narrative Review

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(21), С. 11384 - 11384

Опубликована: Окт. 23, 2024

Diffuse large B-cell lymphoma (DLBCL) is a malignancy of immense biological and clinical heterogeneity. Based on the transcriptomic or genomic approach, several different classification schemes have evolved over years to subdivide DLBCL into clinically (prognostically) relevant subsets, but each leaves unclassified samples. Herein, we outline tumor biology behind actual potential drug targets address challenges drawbacks coupled with their (potential) use. Therapeutic modalities are discussed, including small-molecule inhibitors, naked antibodies, antibody-drug conjugates, chimeric antigen receptors, bispecific antibodies T-cell engagers, immune checkpoint inhibitors. Candidate drugs explored in ongoing trials diverse toxicity issues refractoriness drugs. According literature DLBCL, promise for new therapeutic lies epigenetic alterations, receptor NF-κB pathways. present putative hiding lipid pathways, ferroptosis, gut microbiome that could be used addition immuno-chemotherapy improve general health status patients, thus increasing chance being cured. It may time devote more effort exploring metabolism discover novel druggable targets. We also performed bibliometric knowledge-map analysis published from 2014-2023.

Язык: Английский

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Melatonin supplementation attenuates cuproptosis and ferroptosis in aging cumulus and granulosa cells: potential for improving IVF outcomes in advanced maternal age

Reproductive Biology and Endocrinology, Год журнала: 2024, Номер 22(1)

Опубликована: Ноя. 8, 2024

Advanced maternal age is associated with decreased oocyte quantity and quality in vitro fertilization (IVF) success rates. This study aimed to investigate whether melatonin supplementation can improve IVF outcomes women of advanced by modulating cuproptosis ferroptosis.

Язык: Английский

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