Mitochondrial DNA leakage: underlying mechanisms and therapeutic implications in neurological disorders

Journal of Neuroinflammation, Journal Year: 2025, Volume and Issue: 22(1)

Published: Feb. 7, 2025

Mitochondrial dysfunction is a pivotal instigator of neuroinflammation, with mitochondrial DNA (mtDNA) leakage as critical intermediary. This review delineates the intricate pathways leading to mtDNA release, which include membrane permeabilization, vesicular trafficking, disruption homeostatic regulation, and abnormalities in dynamics. The escaped activates cytosolic sensors, especially cyclic gmp-amp synthase (cGAS) signalling inflammasome, initiating neuroinflammatory cascades via pathways, exacerbating spectrum neurological pathologies. therapeutic promise targeting discussed detail, underscoring necessity for multifaceted strategy that encompasses preservation homeostasis, prevention leakage, reestablishment dynamics, inhibition activation sensors. Advancing our understanding complex interplay between neuroinflammation imperative developing precision interventions disorders.

Language: Английский

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Gallic acid alleviates exercise-induced muscle damage by inhibiting mitochondrial oxidative stress and ferroptosis

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 8, 2025

Language: Английский

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Co-exposure of microcystin and nitrite enhanced spermatogenic disorders: The role of mtROS-mediated pyroptosis and apoptosis

Environment International, Journal Year: 2024, Volume and Issue: 188, P. 108771 - 108771

Published: May 22, 2024

Microcystins (MCs) and nitrites are coexisted in the environment have reproductive toxicity. The combined toxic effect mechanism of MCs nitrite on spermatogenesis remain largely unclear. In present study, co-exposure to microcystin-leucine arginine (MC-LR) sodium (NaNO2) aggravated testicular damage Balb/c mice mitochondrial impairment spermatogonia, Sertoli cells, sperm. Furthermore, MC-LR NaNO2 reduced sperm density with a synergistic effect. addition, synergistically induced oxidative stress system by decreasing superoxide dismutase (SOD) activity glutathione (GSH) levels increasing reactive oxygen species (mtROS) (ROS). More importantly, mitoquidone mesylate (MitoQ), an inhibitor mtROS, blocked NaNO2-induced spermatogonia cell apoptosis inhibiting high expression Bax, Fadd, Caspase-8, cleaved-Caspase-3. On other hand, MitoQ suppressed pyroptosis cells NLRP3, N-GSDMD, cleaved-Caspase-1. Additionally, alleviated co-exposure-induced reduction organ index disorders F1 generation mice. Together, can enhance spermatogenic impairment-mediated germ death. This study emphasizes potential risks reproduction realistic environments highlights new insights into cause treatment disorders.

Language: Английский

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Location and interaction of idebenone and mitoquinone in a membrane similar to the inner mitochondrial membrane. Comparison with ubiquinone 10

Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: 222, P. 211 - 222

Published: June 20, 2024

Oxygen is essential for aerobic life on earth but it also the origin of harmful reactive oxygen species (ROS). Ubiquinone par excellence endogenous cellular antioxidant, a very hydrophobic one. Because that, other molecules have been envisaged, such as idebenone (IDE) and mitoquinone (MTQ), having same redox active benzoquinone moiety higher solubility. We used molecular dynamics to determine location interaction these molecules, both in their oxidized reduced forms, with membrane lipids similar that mitochondria. Both IDE (IDOL) are situated near interface, whereas MTQ (MTQOL) locate position adjacent phospholipid hydrocarbon chains. The quinone moieties ubiquinone 10 (UQ10) UQ10 (UQOL10) contraposition IDE, IDOL, MTQOL, located interphase, isoprenoid chains remained at middle These do not aggregate functional different depths whereby protecting them from ROS effects.

Language: Английский

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Cell–cell communications in the brain of hepatic encephalopathy: The neurovascular unit

Life Sciences, Journal Year: 2025, Volume and Issue: unknown, P. 123413 - 123413

Published: Jan. 1, 2025

Language: Английский

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Targeted downregulation of FIS1 in excitatory neurons within the spinal dorsal horn alleviates neuropathic pain through the mitigation of mitochondrial fragmentation

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 31, 2025

Background: Neuropathic pain has been shown to induce abnormal mitochondrial fission in neurons, yet the analgesic potential of inhibiting this process remains unclear. Our previous studies demonstrated that targeted regulation dynamin-related protein (DRP1) can alleviate neuropathic pain; however, downstream molecular signaling mechanisms remain be elucidated. Methods: To investigate role dynamics pain, we utilized C57BL/6J mice, GAD2-Cre and vGluT2-Cre mice. Mitochondrial network changes states were assessed using GAD2-MITO vGluT2-MITO transgenic mouse models combined with MiNA analysis. Pain thresholds expression levels various molecules spinal dorsal horn (SDH) evaluated through behavioral tests, immunofluorescence, Western blotting. morphology function conditions examined electron microscopy, membrane potential, reactive oxygen species, adenosine triphosphate assays. The effects antioxidant analgesics epigallocatechin gallate (EGCG) Cinnamic Acid on SDH during also investigated. Results: We observed networks both excitatory inhibitory neurons disrupted spared nerve injury as evidenced by models. Specifically, down-regulating FIS1 but not within elicited effects, experiments conducted Additionally, (EGCG), which effectively down-regulates SDH, concurrently inhibited SNI-induced pain. These findings suggest reducing fragmentation

Language: Английский

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FIS1 alleviates neuropathic pain by inhibiting mitochondrial fragmentation

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 6, 2025

Although neuropathic pain leads to abnormal mitochondrial fission in neurons, it remains unclear whether inhibiting has analgesic effects. This study focused on protein 1 (FIS1) investigate its role spared nerve injury (SNI)-induced and the underlying mechanisms. Using MiNA analysis, electron microscopy, membrane potential (MMP), reactive oxygen species (ROS), adenosine triphosphate (ATP) detection, we observed that networks both excitatory inhibitory neurons of spinal dorsal horn (SDH) were disrupted SNI mice, as demonstrated through use specifically constructed GAD2-MITO vGluT2-MITO transgenic mouse models. Furthermore, down-regulating FIS1 but not could exert effects, using vGluT2-Cre mice GAD2-Cre mice. Third, epigallocatechin gallate (EGCG), which was capable horn, concurrently inhibited SNI-induced pain. The above results indicate SDH can alleviate by reducing fragmentation. In addition, improving dysfunction. Our research findings suggest may represent a novel molecular target for treatment

Language: Английский

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Beyond Erectile Dysfunction: Optimization of Vardenafil Dihydrochloride for Hepatic Encephalopathy Prophylaxis using Hybrid Lipid Polymeric Nanoparticles Formulation

Journal of Drug Delivery Science and Technology, Journal Year: 2025, Volume and Issue: unknown, P. 106787 - 106787

Published: March 1, 2025

Language: Английский

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Animal models for complications of cirrhosis

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown, P. 155 - 184

Published: Jan. 1, 2025

Language: Английский

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Optimization of Linagliptin-Loaded Polymersomes via Response Surface Methodology: A Repurposed Therapeutic Strategy for Hepatic Encephalopathy Prevention

Journal of Drug Delivery Science and Technology, Journal Year: 2025, Volume and Issue: unknown, P. 106855 - 106855

Published: March 1, 2025

Language: Английский

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