Glial Perturbation in Metal Neurotoxicity: Implications for Brain Disorders

Neuroglia, Journal Year: 2025, Volume and Issue: 6(1), P. 4 - 4

Published: Jan. 6, 2025

Overexposure of humans to heavy metals and essential poses a significant risk for the development neurological neurodevelopmental disorders. The mechanisms through which these exert their effects include generation reactive oxygen species, mitochondrial dysfunction, activation inflammatory pathways, disruption cellular signaling. function glial cells in brain maintenance homeostasis cannot be overlooked. are particularly susceptible metal-induced neurotoxicity. Accumulation promotes microglial activation, triggering responses that can coincide with other neurotoxicity, inducing alteration synaptic transmission, cognitive deficit, neuronal damage. In this review, we highlighted role dysfunction some selected neurodegenerative diseases We further dive into how exposure such as nickel, manganese, methyl mercury, cadmium, iron, arsenic, lead affect functions microglia, astrocytes, oligodendrocytes they on relation Potential therapeutic interventions use new improved chelating agents antioxidant therapies might approach alleviating perturbations.

Language: Английский

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Cannabidiol prevents LPS-induced inflammation by inhibiting the NLRP3 inflammasome and iNOS activity in BV2 microglia cells via CB2 receptors and PPARγ

Neurochemistry International, Journal Year: 2024, Volume and Issue: 177, P. 105769 - 105769

Published: May 16, 2024

Language: Английский

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Heavy Metal Interactions with Neuroglia and Gut Microbiota: Implications for Huntington’s Disease

Cells, Journal Year: 2024, Volume and Issue: 13(13), P. 1144 - 1144

Published: July 3, 2024

Huntington’s disease (HD) is a rare but progressive and devastating neurodegenerative characterized by involuntary movements, cognitive decline, executive dysfunction, neuropsychiatric conditions such as anxiety depression. It follows an autosomal dominant inheritance pattern. Thus, child who has parent with the mutated huntingtin (mHTT) gene 50% chance of developing disease. Since HTT protein involved in many critical cellular processes, including neurogenesis, brain development, energy metabolism, transcriptional regulation, synaptic activity, vesicle trafficking, cell signaling, autophagy, its aberrant aggregates lead to disruption numerous pathways neurodegeneration. Essential heavy metals are vital at low concentrations; however, higher concentrations, they can exacerbate HD disrupting glial–neuronal communication and/or causing dysbiosis (disturbance gut microbiota, GM), both which neuroinflammation further Here, we discuss detail interactions iron, manganese, copper glial–neuron GM indicate how this knowledge may pave way for development new generation disease-modifying therapies HD.

Language: Английский

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Alpha protein kinase 1 knockout mitigates microglial pyroptosis and cognition deficits in ADP‐heptose‐stimulated mice

The FASEB Journal, Journal Year: 2025, Volume and Issue: 39(3)

Published: Feb. 4, 2025

Abstract Microglial activation and pyroptosis are central to neuroinflammation significantly contribute cognitive decline associated with neurodegenerative diseases. Alpha protein kinase 1 (ALPK1) is recently identified as a critical mediator of inflammatory responses in response ADP‐heptose (a pathogen‐associated molecular pattern). However, its specific role microglial dysfunction remains unclear. In this study, we investigated the effects ALPK1 on function wild‐type (WT) KO mice by intracerebroventricular administration induce neuroinflammation. Cognitive performance was evaluated using behavioral tests (the Y‐Maze, Morris Water Maze, step‐down passive avoidance), while Western blot, immunofluorescence, transmission electron microscopy, enzyme‐linked immunosorbent assay were used evaluate expression markers such NLRP3, Caspase‐1, gasdermin D (GSDMD) vivo vitro. Our results reveal that absence attenuated ADP‐heptose‐induced deficits neuronal injury, inhibited NLRP3/Caspase‐1/GSDMD pathway secretion pro‐inflammatory cytokines IL‐1β IL‐18. Notably, ADP‐heptose‐stimulated conditioned media from primary cells enhanced cell viability, suggesting protective for deficiency supporting health. These findings suggest pivotal impairment, thereby highlighting potential therapeutic target neuroinflammatory disorders.

Language: Английский

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Potential Ameliorating Effects of Fluvoxamine in a Rat Model of Endotoxin-Induced Neuroinflammation: Molecular Aspects Through SIRT-1/GPX-4 and HMGB-1 Signaling

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 15, 2025

Abstract Research on the tissue-protective effects of fluvoxamine (FLV), a selective serotonin reuptake inhibitor, rapidly expands. This study explores FLV’s potential to protect against lipopolysaccharide (LPS)-induced neuroinflammation, key factor in systemic inflammation-related neuronal damage. Four equal groups thirty-two female Wistar Albino rats were created: FLV, LPS-FLV (50 mg/kg intraperitoneal), LPS (5 and control. Both drugs given one dose same day. Tissues from brain cortex, cerebellum, hippocampus taken for histopathology, immunohistochemistry, biochemistry, genetic analysis. In group, histological examinations revealed hyperemia, edema, mild degeneration, death, modest gliosis. Additionally, while apelin total antioxidant status levels reduced, greater oxidative stress index, glial fibrillary acidic protein (GFAP), mammalian target rapamycin (mTOR), oxidant noted. FLV treatment reversed all these findings. Genetic analyses that decreased sirtuin-1 (SIRT-1) glutathione peroxidase 4 (GPX-4) increasing high mobility group box 1 (HMGB-1). parameters, significant result was obtained only with GPX-4. this study, shown have anti-inflammatory neuroprotective through various mechanisms tissues addition its antidepressant effects.

Language: Английский

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Glycyrrhizin alleviates brain injury in necrotizing enterocolitis model mice by suppressing HMGB1/TLR4 pathway

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 150, P. 114294 - 114294

Published: Feb. 18, 2025

Language: Английский

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Neurodegenerative diseases and neuroinflammation-induced apoptosis

Open Life Sciences, Journal Year: 2025, Volume and Issue: 20(1)

Published: Jan. 1, 2025

Abstract Neuroinflammation represents a critical pathway in the brain for clearance of foreign bodies and maintenance homeostasis. When neuroinflammatory process is dysregulate, such as over-activation microglia, which results excessive accumulation free oxygen inflammatory factors brain, among other factors, it can lead to an imbalance homeostasis development various diseases. Recent research has indicated that numerous neurodegenerative diseases closely associated with neuroinflammation. The pathogenesis neuroinflammation intricate, involving alterations genes proteins, well activation inhibition signaling pathways. Furthermore, inflammation result neuronal cell apoptosis, further exacerbate extent disease. This article presents summary recent studies on relationship between apoptosis caused by aim identify link two provide new ideas targets exploring pathogenesis, prevention treatment

Language: Английский

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Unravelling the nexus of stroke and dementia: Deciphering the role of secondary neurodegeneration in orchestrating cognitive decline

Neuroprotection/Neuroprotection (Chichester, England. Print), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

Abstract Stroke is the leading cause of acquired disability. The development acute ischemic stroke treatments, such as mechanical thrombectomy and tissue plasminogen activator, has resulted in more patients surviving initial insult. However, long‐term complications, post‐stroke cognitive impairment (PSCI) dementia (PSD), are at an all‐time high. Notably, 80% survivors suffer from impairment, a history doubles patient's lifetime risk developing dementia. A combination greater life expectancy, increase number strokes young individuals, improved survival have inherently increased years living post‐stroke, highlighting critical need to understand effects stroke, including how pathological changes brain might give rise functional behavioral survivors. Even with this PSCI PSD survivors, understanding itself develops into these conditions remains incomplete. Recently, secondary neurodegeneration (SND) following been linked PSD. SND degeneration regions outside original site. Degeneration sites thought arise due diaschisis infarct core; however, observation pathology multiple without direct connectivity suggests that likely complex. Moreover, hallmarks dementia, deposition neurodegenerative proteins iron, cell death, inflammation blood–brain barrier alterations, all found thalamus, hippocampus, basal ganglia, amygdala prefrontal cortex stroke. Hence, review, we present current context outline remote anatomical molecular may drive conditions.

Language: Английский

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Pathological and Inflammatory Consequences of Aging

Biomolecules, Journal Year: 2025, Volume and Issue: 15(3), P. 404 - 404

Published: March 12, 2025

Aging is a complex, progressive, and irreversible biological process that entails numerous structural functional changes in the organism. These affect all bodily systems, reducing their ability to respond adapt environment. Chronic inflammation one of key factors driving development age-related diseases, ultimately causing substantial decline abilities older individuals. This persistent inflammatory state (commonly known as “inflammaging”) characterized by elevated levels pro-inflammatory cytokines, an increase oxidative stress, perturbation immune homeostasis. Several factors, including cellular senescence, contribute this milieu, thereby amplifying conditions such cardiovascular disease, neurodegeneration, metabolic disorders. Exploring mechanisms chronic aging essential for developing targeted interventions aimed at promoting healthy aging. review explains strong connection between inflammation, highlighting potential therapeutic approaches like pharmacological treatments, dietary strategies, lifestyle changes.

Language: Английский

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Study on the Modulation of NLRP1 by Natural Products in Neurodegenerative Diseases

Natural Product Communications, Journal Year: 2025, Volume and Issue: 20(3)

Published: March 1, 2025

Neuronal pyroptosis is one of the crucial pathogenesis neurodegenerative diseases, and signaling pathway mediated by inflammasome main pyroptosis. Neuroinflammation not only a common feature, but also an essential basis for diagnosis diseases. important pathological feature nervous system diseases such as Alzheimer's disease (AD), Parkinson's (PD). NLRP1 plays role in activating inducing inflammatory response, so development drugs targeting regulation has become reasonable research direction treatment By analyzing current progress which affects process neuronal related Chinese medicine, natural products were docked with targets to find higher activity. The target CB-Dock molecular docking platform. Molecular results showed that silibinin, crocin, hyperoside had excellent binding affinity, most promising potential active compounds AD regulating NLRP1. This paper discusses feasibility rationality medicine on future.

Language: Английский

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