Role of astroglial toll-like receptors (TLRs) in central nervous system infections, injury and neurodegenerative diseases

Brain Behavior and Immunity, Год журнала: 2020, Номер 91, С. 740 - 755

Опубликована: Окт. 8, 2020

Central nervous system (CNS) innate immunity plays essential roles in infections, neurodegenerative diseases, and brain or spinal cord injuries. Astrocytes microglia are the principal cells that mediate CNS. Pattern recognition receptors (PRRs), expressed by astrocytes microglia, sense pathogen-derived endogenous ligands released damaged initiate immune response. Toll-like (TLRs) a well-characterized family of PRRs. The contribution microglial TLR signaling to CNS pathology has been extensively investigated. Even though assume wide variety key functions, information about role astroglial TLRs disease injuries is limited. Because display heterogeneity exhibit phenotypic plasticity depending on effectors present local milieu, they can exert both detrimental beneficial effects. modulators these paradoxical properties. goal current review highlight played diseases. We discuss host defense as well dissemination viral bacterial infections examine link between pathogenesis diseases evidence showing pivotal influence sterile inflammation injury. Finally, we define research questions areas warrant further investigations context astrocytes, TLRs, dysfunction.

Язык: Английский

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Early glycolytic reprogramming controls microglial inflammatory activation

Journal of Neuroinflammation, Год журнала: 2021, Номер 18(1)

Опубликована: Июнь 9, 2021

Microglial activation-mediated neuroinflammation plays an important role in the progression of neurodegenerative diseases. Inflammatory activation microglial cells is often accompanied by a metabolic switch from oxidative phosphorylation to aerobic glycolysis. However, roles and molecular mechanisms glycolysis are not yet fully understood.The anti-inflammatory effects its underlying glycolytic inhibition vitro were examined lipopolysaccharide (LPS) activated BV-2 or primary enzyme-linked immunosorbent assay (ELISA), quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), Western blot, immunoprecipitation, flow cytometry, nuclear factor kappa B (NF-κB) luciferase reporter assays. The neuroprotective inhibitor, 2-deoxoy-D-glucose (2-DG) vivo measured 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-or LPS-induced Parkinson's disease (PD) models immunofluorescence staining, behavior tests, blot analysis.We found that LPS rapidly increased cells, inhibitors (2-DG 3-bromopyruvic acid (3-BPA)), siRNA glucose transporter type 1 (Glut-1), hexokinase (HK) 2 abolished cell activation. Mechanistic studies demonstrated significantly inhibited mechanistic target rapamycin (mTOR), inhibitor factor-kappa kinase subunit beta (IKKβ), NF-kappa-B alpha (IκB-α), degradation IκBα, translocation p65 NF-κB, NF-κB transcriptional activity. In addition, 2-DG acetylation p65/RelA on lysine 310, which mediated NAD-dependent protein deacetylase sirtuin-1 (SIRT1) critical for A coculture study revealed reduced cytotoxicity microglia toward MES23.5 dopaminergic neuron with no direct protective effect. PD model, ameliorated subsequent tyrosine hydroxylase (TH)-positive loss. Furthermore, also death MPTP-induced model.Collectively, our results suggest actively involved Inhibition can ameliorate activation-related neuroinflammatory

Язык: Английский

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Alzheimer’s Disease Pathogenesis: Role of Autophagy and Mitophagy Focusing in Microglia

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(7), С. 3330 - 3330

Опубликована: Март 24, 2021

Alzheimer's disease (AD) is a debilitating neurological disorder, and currently, there no cure for it. Several pathologic alterations have been described in the brain of AD patients, but ultimate causative mechanisms are still elusive. The classic hallmarks AD, including amyloid plaques (Aβ) tau tangles (tau), most studied features AD. Unfortunately, all efforts targeting these pathologies failed to show desired efficacy patients so far. Neuroinflammation impaired autophagy two other main known It has reported that exist long before emergence any clinical manifestation Microglia inflammatory cells considered by many researchers as next hope finding viable therapeutic target Interestingly, it appears mitophagy also changed Inside cells, inflammation interact bidirectional manner. In current review, we briefly discussed an overview on then provided comprehensive discussion role pathways microglia their involvement pathogenesis.

Язык: Английский

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Piezo1 Channels as Force Sensors in Mechanical Force-Related Chronic Inflammation

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Янв. 26, 2022

Mechanical damage is one of the predisposing factors inflammation, and it runs through entire inflammatory pathological process. Repeated or persistent damaging mechanical irritation leads to chronic diseases. The mechanism how forces induce inflammation not fully understood. Piezo1 a newly discovered mechanically sensitive ion channel. channel opens in response stimuli, transducing signals into an cascade cell leading tissue inflammation. A large amount evidence shows that plays vital role occurrence progression This mini-review briefly presents new responds different stresses trigger various tissues. discovery provides insights for treatment diseases related stress. Inhibiting transduction can inhibit improve outcome at early stage. pharmacology has shown bright prospects. development tissue-specific drugs clinical use may be target treating

Язык: Английский

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Urolithin A promotes mitophagy and suppresses NLRP3 inflammasome activation in lipopolysaccharide-induced BV2 microglial cells and MPTP-induced Parkinson's disease model

Neuropharmacology, Год журнала: 2022, Номер 207, С. 108963 - 108963

Опубликована: Янв. 19, 2022

Язык: Английский

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Molecular Mechanisms of Neuroinflammation in Aging and Alzheimer’s Disease Progression

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(3), С. 1869 - 1869

Опубликована: Янв. 18, 2023

Aging is the most prominent risk factor for late-onset Alzheimer’s disease. associates with a chronic inflammatory state both in periphery and central nervous system, evidence thereof mechanisms leading to neuroinflammation being discussed. Nonetheless, significantly enhanced by accumulation of amyloid beta accelerates progression disease through various pathways discussed present review. Decades clinical trials targeting 2 abnormal proteins disease, tau, led many failures. As such, via different strategies could prove valuable therapeutic strategy, although much research still needed identify appropriate time window. Active focusing on identifying early biomarkers help translating these novel from bench bedside.

Язык: Английский

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Galectin-3, a rising star in modulating microglia activation under conditions of neurodegeneration

Cell Death and Disease, Год журнала: 2022, Номер 13(7)

Опубликована: Июль 20, 2022

Abstract The advent of high-throughput single-cell transcriptomic analysis microglia has revealed different phenotypes that are inherently associated with disease conditions. A common feature some these activated is the upregulation galectin-3. Representative examples include disease-associated (DAM) and white-associated (WAM), whose role(s) in neuroprotection/neurotoxicity a matter high interest community. In this review, we summarise main findings demonstrate ability galectin-3 to interact key pattern recognition receptors, including, among others, TLR4 TREM2 importance regulation activation. Finally, discuss increasing evidence supporting involvement lectin neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s Huntington’s amyotrophic lateral sclerosis, multiple traumatic brain injury, stroke.

Язык: Английский

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Oxidative stress and inflammation in the pathogenesis of neurological disorders: Mechanisms and implications

Acta Pharmaceutica Sinica B, Год журнала: 2024, Номер 15(1), С. 15 - 34

Опубликована: Окт. 16, 2024

Neuroprotection is a proactive approach to safeguarding the nervous system, including brain, spinal cord, and peripheral nerves, by preventing or limiting damage nerve cells other components. It primarily defends central system against injury from acute progressive neurodegenerative disorders. Oxidative stress, an imbalance between body's natural defense mechanisms generation of reactive oxygen species, crucial in developing neurological Due its high metabolic rate consumption, brain particularly vulnerable oxidative stress. Excessive ROS damages essential biomolecules, leading cellular malfunction neurodegeneration. Several disorders, Alzheimer's, Parkinson's, Amyotrophic lateral sclerosis, multiple ischemic stroke, are associated with Understanding impact stress these conditions for new treatment methods. Researchers exploring using antioxidants molecules mitigate aiming prevent slow down progression diseases. By understanding intricate interplay scientists hope pave way innovative therapeutic preventive approaches, ultimately improving individuals' living standards.

Язык: Английский

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Neural stem cell-derived exosomes and regeneration: cell-free therapeutic strategies for traumatic brain injury

Stem Cell Research & Therapy, Год журнала: 2023, Номер 14(1)

Опубликована: Авг. 8, 2023

Abstract Regenerative repair of the brain after traumatic injury (TBI) remains an extensive clinical challenge, inspiring intensified interest in therapeutic approaches to explore superior strategies. Exosome therapy is another research hotspot following stem cell alternative therapy. Prior verified that exosomes produced by neural cells can participate physiological and pathological changes associated with TBI have potential neuroregulatory functions. In comparison their parental cells, stability immune tolerance lower tumorigenic risk. addition, they readily penetrate blood‒brain barrier, which makes treatment efficiency transplanted cells. Exosomes secreted present a promising strategy for development novel regenerative therapies. Their tissue regeneration immunomodulatory made them encouraging candidates repair. The review addresses challenges, applications mechanisms regenerating damaged brains.

Язык: Английский

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A New Strategy for the Regulation of Neuroinflammation: Exosomes Derived from Mesenchymal Stem Cells

Cellular and Molecular Neurobiology, Год журнала: 2024, Номер 44(1)

Опубликована: Фев. 19, 2024

Abstract Neuroinflammation is an important pathogenesis of neurological diseases and causes a series physiopathological changes, such as abnormal activation glial cells, neuronal degeneration death, disruption the blood‒brain barrier. Therefore, modulating inflammation may be therapeutic tool for treating diseases. Mesenchymal stem cells (MSCs), pluripotent have great potential due to their regenerative ability, immunity, ability regulate inflammation. However, recent studies shown that MSC-derived exosomes (MSC-Exos) play major role in this process key neuroprotection by regulating neuroglia. This review summarizes progress made neuroinflammation focusing on mechanisms which MSC-Exos are involved regulation through signaling pathways TLR, NF-κB, MAPK, STAT, NLRP3 provide some references subsequent research therapy. Graphical Exosomes derived from MSCs exhibit neuroprotective effects mitigating triggered cells.

Язык: Английский

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