Anti-TNFα and Anti-IL-1β Monoclonal Antibodies Preserve BV-2 Microglial Homeostasis Under Hypoxia by Mitigating Inflammatory Reactivity and ATF4/MAPK-Mediated Apoptosis DOI Creative Commons
Linglin Zhang,

Chaoqiang Guan,

S. Wang

et al.

Antioxidants, Journal Year: 2025, Volume and Issue: 14(3), P. 363 - 363

Published: March 19, 2025

The disruption of microglial homeostasis and cytokine release are critical for neuroinflammation post-injury strongly implicated in retinal neurodegenerative diseases like glaucoma. This study examines responses to chemical hypoxia induced by cobalt chloride (CoCl2) BV-2 murine cells, focusing on signaling pathways proteomic alterations. We assessed the protective effects monoclonal antibodies against TNFα IL-1β. CoCl2 exposure led decreased cell viability, reduced mitochondrial membrane potential, increased lactate dehydrogenase release, elevated reactive oxygen species generation, activation inflammatory pathways, including nitric oxide synthase (iNOS), STAT1, NF-κB/NLRP3. These were significantly mitigated treatment with anti-TNFα anti-IL-1β, suggesting their dual role reducing damage inhibiting reactivity. Additionally, these treatments apoptosis modulating ATF4 p38 MAPK/caspase-3 pathways. Label-free quantitative mass spectrometry-based proteomics Gene Ontology revealed that upregulation proteins primarily involved endoplasmic reticulum catabolic processes, while downregulated associated biosynthesis. Anti-TNFα anti-IL-1β partially restored profile toward normalcy, network analysis identifying heat shock protein family A member 8 (HSPA8) as a central mediator recovery. findings offer insights into pathogenesis hypoxic impairment suggest potential therapeutic targets.

Language: Английский

Crosstalk Between Microglia and Müller Glia in the Age-Related Macular Degeneration: Role and Therapeutic Value of Neuroinflammation DOI Creative Commons
Na Zhao,

Xiao-Na Hao,

Jie-Min Huang

et al.

Aging and Disease, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Age-related macular degeneration (AMD) is a progressive neurodegeneration disease that causes photoreceptor demise and vision impairments. In AMD pathogenesis, the primary death of retinal neurons always leads to activation resident microglia. The migration activated microglia ongoing lesion their morphological transformation from branching ameboid-like are recognized as hallmarks pathogenesis. Activated send signals Müller cells promote them react correspondingly damaging stimulus. type neuroglia maintain normal function neurons, modulating innate inflammatory responses, stabilize structure. can accelerate progression by blood vessels. Therefore, crosstalk between plays homeostatic role in maintaining environment, this interaction complicatedly modulated. particular, mechanism mutual regulation two glia populations complex under pathological conditions. This paper reviews recent findings on during pathology process, with special emphasis its therapeutic potentials.

Language: Английский

Citations

12
Inflammation in the Peripheral Nervous System after Injury DOI Creative Commons

Dandan Gu,

Yiming Xia,

Zihan Ding

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(6), P. 1256 - 1256

Published: June 5, 2024

Nerve injury is a common condition that occurs as result of trauma, iatrogenic injury, or long-lasting stimulation. Unlike the central nervous system (CNS), peripheral (PNS) has strong capacity for self-repair and regeneration. Peripheral nerve results in degeneration distal axons myelin sheaths. Macrophages Schwann cells (SCs) can phagocytose damaged cells. Wallerian (WD) makes whole axon structure degenerate, creating favorable regenerative environment new axons. After macrophages, neutrophils other are mobilized recruited to site necrotic debris. Pro-inflammatory anti-inflammatory factors involved inflammatory response provide microenvironment regeneration regulate effects inflammation on body through relevant signaling pathways. Previously, was thought be detrimental body, but further research shown appropriate promotes regeneration, formation. On contrary, excessive cause tissue damage pathological changes, even lead neurological diseases. Therefore, after various interact with cytokines chemokines promote repair by inhibiting negative harnessing positive specific ways at times. Understanding interaction between neuroinflammation provides several therapeutic ideas improve

Language: Английский

Citations

12
Crosstalk Among Glial Cells in the Blood–Brain Barrier Injury After Ischemic Stroke DOI

Weizhuo Lu,

Jiyue Wen

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 61(9), P. 6161 - 6174

Published: Jan. 27, 2024

Language: Английский

Citations

11
Melatonin alleviates chronic stress-induced hippocampal microglia pyroptosis and subsequent depression-like behaviors by inhibiting Cathepsin B/NLRP3 signaling pathway in rats DOI Creative Commons

Zhicheng Gao,

Kangxin Luo,

Yulin Hu

et al.

Translational Psychiatry, Journal Year: 2024, Volume and Issue: 14(1)

Published: March 27, 2024

Abstract Melatonin improves chronic stress-induced hippocampal damage and depression-like behaviors, but the mechanism needs further study. This study was to explore of melatonin inhibiting microglia pyroptosis. In virtro experiments, improved corticosterone-induced ultrastructure microstructure HAPI cells by pyroptosis, thereby increasing cell survival rate. Protein-protein interaction network molecular autodocking predicted that Cathespin B might be target inhibition NLRP3-mediated inhibited expression. Both Cathepsin inhibitor CA-074Me NLRP3 knockout Similarly, agonist Pazopanib-induced activation B/NLRP3 signaling pathway vivo studies, restraint stress (CRS)-induced alleviated pyroptosis in rats. Inhibition CRS-induced behaviors addition, These results demonstrated could alleviate pathway, improving reveals prevention treatment stress-related encephalopathy.

Language: Английский

Citations

9
Glaucoma Animal Models beyond Chronic IOP Increase DOI Open Access

Teresa Tsai,

Sabrina Reinehr,

Leonie Deppe

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 906 - 906

Published: Jan. 11, 2024

Glaucoma is a complex and multifactorial disease defined as the loss of retinal ganglion cells (RGCs) their axons. Besides an elevated intraocular pressure (IOP), other mechanisms play pivotal role in glaucoma onset progression. For example, it known that excitotoxicity, immunological alterations, ischemia, oxidative stress contribute to neurodegeneration disease. To study these effects discover novel therapeutic approaches, appropriate animal models are needed. In this review, we focus on various beyond IOP. We introduce genetically modified mice, e.g., optineurin E50K knock-in or glutamate aspartate transporter (GLAST)-deficient mouse. Excitotoxicity can be mimicked by injecting analogue N-methyl-D-aspartate intravitreally, which leads rapid RGC degeneration. explore contribution immune system, experimental autoimmune model serve useful tool. Here, immunization with antigens led glaucoma-like damage. The ischemic mechanism inducing high IOP for certain amount time rodents, followed reperfusion. Thereby, damage retina optic nerve occurs rapidly after ischemia/reperfusion. Lastly, discuss importance crush systems normal-tension glaucoma. summary, increase utilized.

Language: Английский

Citations

8
Functional and Phenotypic Diversity of Microglia: Implication for Microglia-Based Therapies for Alzheimer’s Disease DOI Creative Commons
Yijun Xu, Ngan Pan Bennett Au, Chi Him Eddie

et al.

Frontiers in Aging Neuroscience, Journal Year: 2022, Volume and Issue: 14

Published: May 26, 2022

Alzheimer’s disease (AD) is a progressive neurodegenerative and closely associated with the accumulation of β-amyloid (Aβ) neurofibrillary tangles (NFTs). Apart from Aβ NFT pathologies, AD patients also exhibit widespread microglial activation in various brain regions elevated production pro-inflammatory cytokines, phenomenon known as neuroinflammation. In healthy central nervous system, microglia adopt ramified, “surveying” phenotype compact cell bodies elongated processes. AD, presence pathogenic proteins such extracellular plaques hyperphosphorylated tau, induce transformation ramified into amoeboid microglia. Ameboid are highly phagocytic immune cells actively secrete cascade cytokines chemokines. However, ability gradually declines age, thus clearance becomes ineffective, leading to tau aging brain. The further augments neuroinflammatory responses sustains excessive induces massive loss functional synapses neurons, worsening condition AD. More recently, identification subset by transcriptomic studies, namely disease-associated (DAM), transition homeostatic DAM TREM2-dependent acquire state during progression Recent in-depth analysis identifies ApoE Trem2 major risk factors for pathogenesis. this review, we summarize current understandings roles age-dependent neuroinflammation pathogenesis To end, exponential growth data provides solid foundation silico drug screening gains insight development microglia-based therapeutic interventions

Language: Английский

Citations

34
TRIM28 Fosters Microglia Ferroptosis via Autophagy Modulation to Enhance Neuropathic Pain and Neuroinflammation DOI
Jian Tang, Qi Chen,

Li Xiang

et al.

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 61(11), P. 9459 - 9477

Published: April 22, 2024

Language: Английский

Citations

7
Microglial mediators in autoimmune Uveitis: Bridging neuroprotection and neurotoxicity DOI
Monika Sharma, Pankaj Pal, Sukesh Kumar Gupta

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 136, P. 112309 - 112309

Published: May 29, 2024

Language: Английский

Citations

7
Irisin attenuates acute glaucoma-induced neuroinflammation by activating microglia-integrin αVβ5/AMPK and promoting autophagy DOI
Qiuxiang Zhang,

Sifei Xiang,

Xi Chen

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 138, P. 112545 - 112545

Published: July 1, 2024

Language: Английский

Citations

6
Optic nerve diseases and regeneration: How far are we from the promised land? DOI
Ling‐Ping Cen, Kevin K. Park, Kwok‐Fai So

et al.

Clinical and Experimental Ophthalmology, Journal Year: 2023, Volume and Issue: 51(6), P. 627 - 641

Published: June 15, 2023

Abstract The retinal ganglion cells (RGCs) are the sole output neurons that connect information from retina to brain. Optic neuropathies such as glaucoma, trauma, inflammation, ischemia and hereditary optic neuropathy can cause RGC loss axon damage, lead partial or total of vision, which is an irreversible process in mammals. accurate diagnoses crucial for timely treatments prevent irrevocable RGCs loss. After severe ON damage neuropathies, promoting regeneration vital restoring vision. Clearance neuronal debris, decreased intrinsic growth capacity, presence inhibitory factors have been shown contribute failure post‐traumatic CNS regeneration. Here, we review current understanding manifestations various common neuropathies. We also summarise known mechanisms survival mammals, including specific signalling pathways, key transcription factors, reprogramming genes, inflammation‐related stem cell therapy, combination therapies. Significant differences subtypes regenerative capacity after injury found. Finally, highlight developmental states non‐mammalian species capable regenerating axons injury, cellular state neural repair.

Language: Английский

Citations

15