Immunological dimensions of neuroinflammation and microglial activation: exploring innovative immunomodulatory approaches to mitigate neuroinflammatory progression

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 8, 2024

The increasing life expectancy has led to a higher incidence of age-related neurodegenerative conditions. Within this framework, neuroinflammation emerges as significant contributing factor. It involves the activation microglia and astrocytes, leading release pro-inflammatory cytokines chemokines infiltration peripheral leukocytes into central nervous system (CNS). These instances result in neuronal damage neurodegeneration through activated nucleotide-binding domain leucine-rich repeat containing (NLR) family pyrin protein 3 (NLRP3) nuclear factor kappa B (NF-kB) pathways decreased erythroid 2-related 2 (Nrf2) activity. Due limited effectiveness regarding inhibition neuroinflammatory targets using conventional drugs, there is challenging growth search for innovative therapies alleviating CNS diseases or even before their onset. Our results indicate that interventions focusing on Interleukin-Driven Immunomodulation, Chemokine (CXC) Receptor Signaling Expression, Cold Exposure, Fibrin-Targeted strategies significantly promise mitigate processes. approaches demonstrate potential anti-neuroinflammatory effects, addressing conditions such Multiple Sclerosis, Experimental autoimmune encephalomyelitis, Parkinson’s Disease, Alzheimer’s Disease. While findings are promising, immunomodulatory often face limitations due Immune-Related Adverse Events. Therefore, conduction randomized clinical trials matter mandatory, will pave way promising future development new medicines with specific therapeutic targets.

Language: Английский

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The NF-κB signaling system in the immunopathogenesis of inflammatory bowel disease

Science Signaling, Journal Year: 2024, Volume and Issue: 17(818)

Published: Jan. 9, 2024

Inflammatory bowel disease (IBD) is an idiopathic, chronic condition characterized by episodes of inflammation in the gastrointestinal tract. The nuclear factor κB (NF-κB) system describes a family dimeric transcription factors. Canonical NF-κB signaling stimulated and enhances inflammation, whereas noncanonical contributes to immune organogenesis. Dysregulation factors drives various inflammatory pathologies, including IBD. Signals from many sensors activate subunits intestine, which maintain equilibrium between local microbiota host responses. Genetic association studies patients with IBD preclinical mouse models confirm importance defense gut. Other have investigated roles these intestinal barrier function gut pathologies associated modulates innate adaptive responses production immunoregulatory proteins, anti-inflammatory cytokines, antimicrobial peptides, other tolerogenic intestine. Furthermore, genetic revealed critical cell type–specific for proteins homeostasis, restitution that contribute etiopathology IBD-associated manifestations. Here, we summarize our knowledge pathways, are activated different types specific ligands, their cross-talk, fueling aberrant inflammation. We argue in-depth understanding mechanisms may hold key identifying predictive or prognostic biomarkers developing better therapeutics against pathologies.

Language: Английский

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Prospects and challenges for the application of tissue engineering technologies in the treatment of bone infections

Bone Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: May 14, 2024

Osteomyelitis is a devastating disease caused by microbial infection in deep bone tissue. Its high recurrence rate and impaired restoration of deficiencies are major challenges treatment. Microbes have evolved numerous mechanisms to effectively evade host intrinsic adaptive immune attacks persistently localize the host, such as drug-resistant bacteria, biofilms, persister cells, intracellular small colony variants (SCVs). Moreover, microbial-mediated dysregulation microenvironment impedes regeneration process, leading defect repair. Despite advances surgical strategies drug applications for treatment infections within last decade, remain clinical management. The development application tissue engineering materials provided new infections, but comprehensive review their research progress lacking. This discusses critical pathogenic microbes skeletal system immunomodulatory effects on regeneration, highlights prospects technologies infections. It will inform translation antimicrobial repair management

Language: Английский

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NF-κB as an Inducible Regulator of Inflammation in the Central Nervous System

Cells, Journal Year: 2024, Volume and Issue: 13(6), P. 485 - 485

Published: March 11, 2024

The NF-κB (nuclear factor K-light-chain-enhancer of activated B cells) transcription family is critical for modulating the immune proinflammatory response throughout body. During resting state, inactive sequestered by IκB in cytoplasm. proteasomal degradation activates NF-κB, mediating its translocation into nucleus to act as a nuclear upregulation genes. Stimuli that initiate activation are diverse but canonically attributed cytokines and chemokines. Downstream effects cell type-specific and, majority cases, result pro-inflammatory cascades. Acting primary responders central nervous system, microglia exhibit upon pathological conditions. Under such circumstances, microglial crosstalk with other types system can induce death, further exacerbating disease pathology. In this review, we will emphasize role triggering neuroinflammation mediated microglia.

Language: Английский

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Uncovering the Power of GPR18 Signalling: How RvD2 and Other Ligands Could Have the Potential to Modulate and Resolve Inflammation in Various Health Disorders

Molecules, Journal Year: 2024, Volume and Issue: 29(6), P. 1258 - 1258

Published: March 12, 2024

The resolution of inflammation is the primary domain specialised pro-resolving mediators (SPMs), which include resolvins, protectins, and their forms synthesised under influence aspirin maresins. role these SPMs has been discussed by many authors in literature, with particular reference to neuroinflammation significant neurological disorders. This review discusses G protein-coupled receptor 18 (GPR18), resolvin D2 (RvD2) activity, GPR18-RvD2 signalling axis, as well small molecule ligands GPR18 various health disorders (brain injuries, neuropathic pain, neurodegenerative/cardiometabolic/cardiovascular/gastrointestinal diseases, peritonitis, periodontitis, asthma lung inflammation, Duchenne muscular dystrophy, SARS-CoV-2-induced placenta idea biological intervention through modulating attracting growing attention because its great therapeutic potential. With this paper, we aimed present a comprehensive most recent perform constructive view data, point out research gaps.

Language: Английский

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Resveratrol-driven macrophage polarization: unveiling mechanisms and therapeutic potential

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 13, 2025

Resveratrol, a polyphenolic compound known for its diverse biological activities, has demonstrated multiple pharmacological effects, including anti-inflammatory, anti-aging, anti-diabetic, anti-cancer, and cardiovascular protective properties. Recent studies suggest that these effects are partly mediated through the regulation of macrophage polarization, wherein macrophages differentiate into pro-inflammatory M1 or anti-inflammatory M2 phenotypes. Our review highlights how resveratrol modulates polarization various signaling pathways to achieve therapeutic effects. For example, can activate senescence-associated secretory phenotype (SASP) pathway inhibit signal transducer activator transcription (STAT3) sphingosine-1-phosphate (S1P)-YAP axes, promoting suppressing thereby inhibiting tumor growth. Conversely, it promote suppress by NF-κB activating PI3K/Akt AMP-activated protein kinase (AMPK) pathways, thus alleviating inflammatory responses. Notably, effect on is concentration-dependent; moderate concentrations tend while higher may favor polarization. This concentration dependence offers new perspectives clinical treatment but also underscores necessity precise dosage control when using resveratrol. In summary, exhibits significant potential in regulating treating related diseases.

Language: Английский

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Molecular Mechanisms in Pathophysiology of Mucopolysaccharidosis and Prospects for Innovative Therapy

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 1113 - 1113

Published: Jan. 17, 2024

Mucopolysaccharidoses (MPSs) are a group of inborn errors the metabolism caused by deficiency in lysosomal enzymes required to break down molecules called glycosaminoglycans (GAGs). These GAGs accumulate over time various tissues and disrupt multiple biological systems, including catabolism other substances, autophagy, mitochondrial function. pathological changes ultimately increase oxidative stress activate innate immunity inflammation. We have described pathophysiology MPS activated inflammation this paper, starting with accumulating primary storage materials, GAGs. At initial stage GAG accumulation, affected tissues/cells reversibly but progress irreversibly to: (1) disruption substrate degradation pathogenic function, (2) cellular dysfunction, secondary/tertiary accumulation (toxins such as GM2 or GM3 ganglioside, etc.), inflammatory process, (3) progressive tissue/organ damage cell death (e.g., skeletal dysplasia, CNS impairment, etc.). For current future treatment, several potential treatments for that can penetrate blood–brain barrier bone been proposed and/or clinical trials, targeting peptides molecular Trojan horses monoclonal antibodies attached via receptor-mediated transport. Gene therapy trials AAV, ex vivo LV, Sleeping Beauty transposon system underway innovative therapeutic options. In addition, possible immunomodulatory reagents suppress symptoms summarized review.

Language: Английский

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Revealing the role of SPP1+ macrophages in glioma prognosis and therapeutic targeting by investigating tumor-associated macrophage landscape in grade 2 and 3 gliomas

Cell & Bioscience, Journal Year: 2024, Volume and Issue: 14(1)

Published: March 21, 2024

Abstract Background Glioma is a highly heterogeneous brain tumor categorized into World Health Organization (WHO) grades 1–4 based on its malignancy. The suppressive immune microenvironment of glioma contributes significantly to unfavourable patient outcomes. However, the cellular composition and their complex interplays within environment remain poorly understood, reliable prognostic markers elusive. Therefore, in-depth exploration (TME) identification predictive are crucial for improving clinical management patients. Results Our analysis single-cell RNA-sequencing data from samples unveiled immunosuppressive role tumor-associated macrophages (TAMs), mediated through intricate interactions with cells lymphocytes. We also discovered heterogeneity TAMs, among which group TAMs named TAM-SPP1 demonstrated significant association Epidermal Growth Factor Receptor ( EGFR ) amplification, impaired T cell response survival Furthermore, by leveraging genomic transcriptomic Cancer Genome Atlas (TCGA) dataset, two distinct molecular subtypes different constitution status outcomes were identified. Exploiting differences between these subtypes, we developed four-gene-based model. This model displayed strong associations an elevated level could be used predict anti-tumor prognosis in Conclusion findings illuminated mechanisms that shape gliomas, providing novel insights potential therapeutic targets. holds promise predicting immunotherapy assisting more precise risk stratification Graphical abstract

Language: Английский

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Glutathione‑degrading enzymes in the complex landscape of tumors (Review)

International Journal of Oncology, Journal Year: 2024, Volume and Issue: 65(1)

Published: June 3, 2024

Glutathione (GSH)‑degrading enzymes are essential for starting the first stages of GSH degradation. These include extracellular γ‑glutamyl transpeptidase (GGT) and intracellular GSH‑specific γ‑glutamylcyclotransferase 1 (ChaC1) 2. cellular activities, such as immune response, differentiation, proliferation, homeostasis regulation programmed cell death. Tumor tissue frequently exhibits abnormal expression GSH‑degrading enzymes, which has a key impact on development spread malignancies. The present review summarizes gene protein structure, catalytic activity their vital roles in tumor (including oxidative endoplasmic reticulum stress, control death, promotion inflammation tumorigenesis modulation drug resistance cells) potential role diagnostic biomarkers therapeutic targets.

Language: Английский

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Anti-inflammatory mechanism of Apolipoprotein A-I

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: July 8, 2024

Apolipoprotein A-I(ApoA-I) is a member of blood apolipoproteins, it the main component High density lipoprotein(HDL). ApoA-I undergoes series complex processes from its generation to composition as spherical HDL. It not only has cholesterol reversal transport function, but also function in modulating inflammatory response. exerts anti-inflammatory effects mainly by regulating functions immune cells, such monocytes/macrophages, dendritic neutrophils, and T lymphocytes. modulates vascular endothelial cells adipocytes. Additionally, directly against pathogenic microorganisms or their products. Intensive research on will hopefully lead better diagnosis treatment diseases.

Language: Английский

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