Transcriptomics-based analysis of co-exposure of cadmium (Cd) and 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) indicates mitochondrial dysfunction induces NLRP3 inflammasome and inflammatory cell death in renal tubular epithelial cells DOI Creative Commons
Yi Zhang, Bo Hu, Xiaolan Qian

и другие.

Ecotoxicology and Environmental Safety, Год журнала: 2022, Номер 241, С. 113790 - 113790

Опубликована: Июнь 23, 2022

Environmental pollution often releases multiple contaminants resulting in as yet largely uncharacterized additive toxicities. Cadmium (Cd) is a widespread pollutant that induces nephrotoxicity animal models and humans. However, the combined effect of Cd causing with 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), typical congener polybrominated diphenyl ethers (PBDEs), has not been evaluated mechanisms are completely clear. Here, we applied transcriptome sequencing analysis to investigate toxicity BDE-47 renal tubular epithelial cell lines HKCs. or exposure decreased viability dose-dependent manner, exhibited swelling rounding similar necrosis, which was exacerbated by co-exposure. Transcriptomic revealed 2191, 1331 3787 differentially-expressed genes following treatment Cd, co-exposure, respectively. Interestingly, functional annotation enrichment analyses showed involvement pathways for oxidative stress, NOD-, LRR- pyrin domain-containing protein 3 (NLRP3) inflammasome inflammatory death all three treatments. Examination indices mitochondrial function stress HKC cells levels reactive oxygen species (ROS), malondialdehyde (MDA) intracellular calcium ion concentration [Ca2+]i were elevated, while superoxide dismutase (SOD) membrane potential (MMP) decreased. The ratio apoptotic necrotic lactate dehydrogenase (LDH) release increased exposure, aggravated attenuated ROS scavenger N-Acetyl-L-cysteine (NAC). NLRP3 pyroptosis pathway-related NLRP3, adaptor molecule apoptosis-associated speck-like (ASC), caspase-1, interleukin-18 (IL-18) IL-1β gasdermin D (GSDMD) down-regulated, cleaved caspase-1 GSDMD increased, most relieved NAC. Our data demonstrate dysfunction triggers GSDMD-dependent leading nephrotoxicity, co-exposure exacerbates this effect, could be inhibiting ROS. This study provides further mechanistic understanding kidney damage, impact worthy concern should considered improve accuracy environmental health assessment.

Язык: Английский

Urolithin A suppresses RANKL-induced osteoclastogenesis and postmenopausal osteoporosis by, suppresses inflammation and downstream NF-κB activated pyroptosis pathways DOI

Huaqiang Tao,

Wenming Li, Wei Zhang

и другие.

Pharmacological Research, Год журнала: 2021, Номер 174, С. 105967 - 105967

Опубликована: Ноя. 3, 2021

Язык: Английский

Процитировано

120
Mitochondrial dysfunction in microglia: a novel perspective for pathogenesis of Alzheimer’s disease DOI Creative Commons
Yun Li, Xiaohuan Xia, Yi Wang

и другие.

Journal of Neuroinflammation, Год журнала: 2022, Номер 19(1)

Опубликована: Окт. 6, 2022

Abstract Alzheimer's disease (AD) is the most common neurodegenerative in elderly globally. Emerging evidence has demonstrated microglia-driven neuroinflammation as a key contributor to onset and progression of AD, however, mechanisms that mediate remain largely unknown. Recent studies have suggested mitochondrial dysfunction including DNA (mtDNA) damage, metabolic defects, quality control (QC) disorders precedes microglial activation subsequent neuroinflammation. Therefore, an in-depth understanding relationship between AD important unveil pathogenesis develop effective approaches for early diagnosis treatment. In this review, we summarized current progress roles mtDNA, metabolism, QC changes provide comprehensive thoughts targeting mitochondria potential therapeutic strategies AD.

Язык: Английский

Процитировано

82
Mitochondrial dysfunction in chronic neuroinflammatory diseases (Review) DOI Creative Commons
Pei Qin,

Ye Sun,

Liya Li

и другие.

International Journal of Molecular Medicine, Год журнала: 2024, Номер 53(5)

Опубликована: Апрель 2, 2024

Chronic neuroinflammation serves a key role in the onset and progression of neurodegenerative disorders. Mitochondria serve as central regulators neuroinflammation. In addition to providing energy cells, mitochondria also participate immunoinflammatory response disorders including Alzheimer's disease, Parkinson's multiple sclerosis epilepsy, by regulating processes such cell death inflammasome activation. Under inflammatory conditions, mitochondrial oxidative stress, epigenetics, dynamics calcium homeostasis imbalance may underlying regulatory mechanisms for these diseases. Therefore, investigating related dysfunction result therapeutic strategies against chronic neurodegeneration. The present review summarizes neuroinflammatory diseases current treatment approaches that target

Язык: Английский

Процитировано

16
Mitochondrial DNA leakage: underlying mechanisms and therapeutic implications in neurological disorders DOI Creative Commons
Guangming Zhang,

Huayuan Wei,

Anliu Zhao

и другие.

Journal of Neuroinflammation, Год журнала: 2025, Номер 22(1)

Опубликована: Фев. 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.

Язык: Английский

Процитировано

3
Glaucomatous optic neuropathy: Mitochondrial dynamics, dysfunction and protection in retinal ganglion cells DOI Creative Commons

Won‐Kyu Ju,

Guy Perkins, Keunyoung Kim

и другие.

Progress in Retinal and Eye Research, Год журнала: 2022, Номер 95, С. 101136 - 101136

Опубликована: Ноя. 16, 2022

Glaucoma is a leading cause of irreversible blindness worldwide and characterized by slow, progressive, multifactorial degeneration retinal ganglion cells (RGCs) their axons, resulting in vision loss. Despite its high prevalence individuals 60 years age older, the causing factors contributing to glaucoma progression are currently not well characterized. Intraocular pressure (IOP) only proven treatable risk factor. However, lowering IOP insufficient for preventing disease progression. One significant interests pathogenesis understanding structural functional impairment mitochondria RGCs axons synapses. Glaucomatous such as elevation, aging, genetic variation, neuroinflammation, neurotrophic factor deprivation, vascular dysregulation, potential inducers mitochondrial dysfunction glaucoma. Because oxidative phosphorylation stress-mediated associated with glaucomatous RGCs, underlying mechanisms relationship between alterations would be beneficial developing mitochondria-related neuroprotection synapses against neurodegeneration. Here, we review current studies focusing on dynamics-based therapeutic strategies protect

Язык: Английский

Процитировано

65
Spotlight on pyroptosis: role in pathogenesis and therapeutic potential of ocular diseases DOI Creative Commons

Meini Chen,

Rong Rong, Xiaobo Xia

и другие.

Journal of Neuroinflammation, Год журнала: 2022, Номер 19(1)

Опубликована: Июль 14, 2022

Pyroptosis is a programmed cell death characterized by swift plasma membrane disruption and subsequent release of cellular contents pro-inflammatory mediators (cytokines), including IL-1β IL-18. It differs from other types such as apoptosis, autophagy, necroptosis, ferroptosis, NETosis in terms its morphology mechanism. As recently discovered form death, pyroptosis has been demonstrated to be involved the progression multiple diseases. Recent studies have also suggested that linked various ocular In this review, we systematically summarized discussed recent scientific discoveries involvement common diseases, diabetic retinopathy, age-related macular degeneration, AIDS-related human cytomegalovirus retinitis, glaucoma, dry eye disease, keratitis, uveitis, cataract. We organized new emerging evidence suggesting signaling pathways may potential therapeutic targets hoping provide summary overall intervention strategies relevant multi-dimensional evaluations for well offer valuable ideas further research development perspective pyroptosis.

Язык: Английский

Процитировано

64
Retinal Glutamate Neurotransmission: From Physiology to Pathophysiological Mechanisms of Retinal Ganglion Cell Degeneration DOI Creative Commons
Isabella Boccuni, Richard Fairless

Life, Год журнала: 2022, Номер 12(5), С. 638 - 638

Опубликована: Апрель 25, 2022

Glutamate neurotransmission and metabolism are finely modulated by the retinal network, where efficient processing of visual information is shaped differential distribution composition glutamate receptors transporters. However, disturbances in homeostasis can result excitotoxicity, a major initiating factor common neurodegenerative diseases. Within retina, excitotoxicity impair transmission degeneration neuronal populations, including ganglion cells (RGCs). The vulnerability RGCs observed not just as diseases but has also been ascribed to other peripheral In this review, we describe contribution different transporters this. particular, focus on

Язык: Английский

Процитировано

52
Mitochondrial Quality Control: A Pathophysiological Mechanism and Therapeutic Target for Stroke DOI Creative Commons
Miaoxian Yang,

Yu He,

Shuixiang Deng

и другие.

Frontiers in Molecular Neuroscience, Год журнала: 2022, Номер 14

Опубликована: Янв. 28, 2022

Stroke is a devastating disease with high mortality and disability rates. Previous research has established that mitochondria, as major regulators, are both influenced by stroke, further regulated the development of poststroke injury. Mitochondria involved in several biological processes such energy generation, calcium homeostasis, immune response, apoptosis regulation, reactive oxygen species (ROS) generation. Meanwhile, mitochondria can evolve into various quality control systems, including mitochondrial dynamics (fission fusion) mitophagy, to maintain homeostasis network. Various activities fission fusion associated integrity neurological injury after stroke. Additionally, proper mitophagy seems be neuroprotective for its effect on eliminating damaged while excessive disturbs generation mitochondria-associated signal pathways. The balance between more crucial than absolute level each process. A neurovascular unit (NVU) multidimensional system which cells release multiple mediators regulate diverse signaling pathways across whole network way dynamic interaction. turbulence (MQC) could lead NVU dysfunctions, neuron death, neuroglial activation, blood–brain barrier (BBB) disruption, neuroinflammation. However, exact changes effects MQC stroke have yet fully illustrated. In this review, we will discuss updated mechanisms pathophysiology We highlight regulation potential therapeutic target ischemic hemorrhagic

Язык: Английский

Процитировано

41
Gene expression data analysis using Hellinger correlation in weighted gene co-expression networks (WGCNA) DOI Creative Commons
Tianjiao Zhang, Garry Wong

Computational and Structural Biotechnology Journal, Год журнала: 2022, Номер 20, С. 3851 - 3863

Опубликована: Янв. 1, 2022

Weighted gene co-expression network analysis (WGCNA) is used to detect clusters with highly correlated genes. Measurements of correlation most typically rely on linear relationships. However, a relationship does not always model pairwise functional-related dependence between In this paper, we first compared 6 different methods in their ability capture complex genes three tissues. Next, gene-pairwise coefficient results and corresponding WGCNA results. Finally, applied recently proposed method, Hellinger correlation, as more sensitive measurement WGCNA. To test constructed networks containing modules from RNA-seq data human frontal cortex Alzheimer's disease patients. the generality, also microarray set cortex, single cell prefrontal temporal GTEx heart. The method captures essentially similar other correlations WGCNA, but provides additional new functional relationships exemplified by uncovering link inflammation mitochondria function. We validated sequencing sets dataset cortex. observed that enables detection non-linear biologically meaningful among robustly complementary approach Thus, application flexible modelling expression uncovers novel

Язык: Английский

Процитировано

39
Mitophagy in the retina: Viewing mitochondrial homeostasis through a new lens DOI Creative Commons
Juan Ignacio Jiménez‐Loygorri, Rocío Benítez‐Fernández, Álvaro Viedma-Poyatos

и другие.

Progress in Retinal and Eye Research, Год журнала: 2023, Номер 96, С. 101205 - 101205

Опубликована: Июль 15, 2023

Mitochondrial function is key to support metabolism and homeostasis in the retina, an organ that has one of highest metabolic rates body-wide constantly exposed photooxidative damage external stressors. Mitophagy selective autophagic degradation mitochondria within lysosomes, can be triggered by distinct stimuli such as mitochondrial or hypoxia. Here, we review importance mitophagy retinal physiology pathology. In developing essential for reprogramming differentiation retina ganglion cells (RGCs). basal conditions, acts a quality control mechanism, maintaining healthy pool meet cellular demands. We summarize different autophagy- mitophagy-deficient mouse models described literature, discuss potential role dysregulation diseases glaucoma, diabetic retinopathy, retinitis pigmentosa, age-related macular degeneration. Finally, provide overview methods used monitor vitro, ex vivo, vivo. This highlights important sustaining visual function, its putative therapeutic target other diseases.

Язык: Английский

Процитировано

31