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 Interplay between Ferroptosis and Neuroinflammation in Central Neurological Disorders

Antioxidants, Journal Year: 2024, Volume and Issue: 13(4), P. 395 - 395

Published: March 26, 2024

Central neurological disorders are significant contributors to morbidity, mortality, and long-term disability globally in modern society. These encompass neurodegenerative diseases, ischemic brain traumatic injury, epilepsy, depression, more. The involved pathogenesis is notably intricate diverse. Ferroptosis neuroinflammation play pivotal roles elucidating the causes of cognitive impairment stemming from these diseases. Given concurrent occurrence ferroptosis due metabolic shifts such as iron ROS, well their critical central nervous disorders, investigation into co-regulatory mechanism has emerged a prominent area research. This paper delves mechanisms along with interrelationship. It specifically emphasizes core molecules within shared pathways governing neuroinflammation, including SIRT1, Nrf2, NF-κB, Cox-2, iNOS/NO·, how different immune cells structures contribute dysfunction through mechanisms. Researchers’ findings suggest that mutually promote each other may represent key factors progression disorders. A deeper comprehension common pathway between cellular holds promise for improving symptoms prognosis related

Language: Английский

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Tissue macrophages: origin, heterogenity, biological functions, diseases and therapeutic targets

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: March 7, 2025

Abstract Macrophages are immune cells belonging to the mononuclear phagocyte system. They play crucial roles in defense, surveillance, and homeostasis. This review systematically discusses types of hematopoietic progenitors that give rise macrophages, including primitive progenitors, erythro-myeloid stem cells. These have distinct genetic backgrounds developmental processes. Accordingly, macrophages exhibit complex diverse functions body, phagocytosis clearance cellular debris, antigen presentation, response, regulation inflammation cytokine production, tissue remodeling repair, multi-level regulatory signaling pathways/crosstalk involved homeostasis physiology. Besides, tumor-associated a key component TME, exhibiting both anti-tumor pro-tumor properties. Furthermore, functional status is closely linked development various diseases, cancer, autoimmune disorders, cardiovascular disease, neurodegenerative metabolic conditions, trauma. Targeting has emerged as promising therapeutic strategy these contexts. Clinical trials macrophage-based targeted drugs, immunotherapies, nanoparticle-based therapy were comprehensively summarized. Potential challenges future directions targeting also been discussed. Overall, our highlights significance this versatile cell human health which expected inform research clinical practice.

Language: Английский

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Redox regulation: mechanisms, biology and therapeutic targets in diseases

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: March 7, 2025

Redox signaling acts as a critical mediator in the dynamic interactions between organisms and their external environment, profoundly influencing both onset progression of various diseases. Under physiological conditions, oxidative free radicals generated by mitochondrial respiratory chain, endoplasmic reticulum, NADPH oxidases can be effectively neutralized NRF2-mediated antioxidant responses. These responses elevate synthesis superoxide dismutase (SOD), catalase, well key molecules like nicotinamide adenine dinucleotide phosphate (NADPH) glutathione (GSH), thereby maintaining cellular redox homeostasis. Disruption this finely tuned equilibrium is closely linked to pathogenesis wide range Recent advances have broadened our understanding molecular mechanisms underpinning dysregulation, highlighting pivotal roles genomic instability, epigenetic modifications, protein degradation, metabolic reprogramming. findings provide foundation for exploring regulation mechanistic basis improving therapeutic strategies. While antioxidant-based therapies shown early promise conditions where stress plays primary pathological role, efficacy diseases characterized complex, multifactorial etiologies remains controversial. A deeper, context-specific signaling, particularly redox-sensitive proteins, designing targeted aimed at re-establishing balance. Emerging small molecule inhibitors that target specific cysteine residues proteins demonstrated promising preclinical outcomes, setting stage forthcoming clinical trials. In review, we summarize current intricate relationship disease also discuss how these insights leveraged optimize strategies practice.

Language: Английский

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Neurosyphilis: insights into its pathogenesis, susceptibility, diagnosis, treatment, and prevention

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

Published: Jan. 11, 2024

Background and aim Invasion of the central nervous system by Treponema pallidum can occur at any stage syphilis. In event that T. is not cleared promptly, certain individuals may experience progression to neurosyphilis, which manifests as cognitive behavioral abnormalities, limb paralysis, potentially fatal outcomes. Early identification or prevention neurosyphilis therefore crucial. The this paper conduct a critical narrative review latest information focusing exclusively pathogenesis clinical management neurosyphilis. Methodology To compile review, we have conducted electronic literature searches from PubMed database relating Priority was given studies published past 10 years (from 2013 2023) other if they were significant importance 1985 2012), including whole genome sequencing results, cell structure , history genotyping, related topics. These are classic reflect developmental process. Results Neurosyphilis has garnered global attention, yet susceptibility condition remain under investigation. Cerebrospinal fluid examination plays an important role in diagnosis but lacks gold standard. Intravenous aqueous crystalline penicillin G continues be recommended therapeutic approach for Considering its sustained prominence, it imperative develop novel public health tactics order manage resurgence Conclusion This gives updated description with special emphasis on pathogenesis, susceptibility, diagnosis, treatment, prevention.

Language: Английский

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Neurodegenerative diseases and catechins: (−)-epigallocatechin-3-gallate is a modulator of chronic neuroinflammation and oxidative stress

Frontiers in Nutrition, Journal Year: 2024, Volume and Issue: 11

Published: Aug. 1, 2024

Catechins, a class of phytochemicals found in various fruits and tea leaves, have garnered attention for their diverse health-promoting properties, including potential combating neurodegenerative diseases. Among these catechins, (-)-epigallocatechin-3-gallate (EGCG), the most abundant polyphenol green tea, has emerged as promising therapeutic agent due to its potent antioxidant anti-inflammatory effects. Chronic neuroinflammation oxidative stress are key pathological mechanisms diseases such Alzheimer's disease (AD) Parkinson's (PD). EGCG neuroprotective efficacy scavenging free radicals, reducing attenuating neuroinflammatory processes. This review discusses molecular EGCG's anti-oxidative chronic neuroinflammation, emphasizing effects on autoimmune responses, neuroimmune system interactions, focusing related AD PD. By elucidating action impact processes, this underscores intervention AD, PD, possibly other Overall, emerges natural compound stress, offering novel avenues strategies treatment disorders.

Language: Английский

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Engineered Extracellular Vesicle-Based Nanoformulations That Coordinate Neuroinflammation and Immune Homeostasis, Enhancing Parkinson’s Disease Therapy

ACS Nano, Journal Year: 2024, Volume and Issue: 18(34), P. 23014 - 23031

Published: Aug. 15, 2024

Although conventional intervention to microglia can mitigate neuroinflammation in the short term, immune disorders by peripheral inflammatory cells infiltrate continuously, resulting an overactivated microenvironment of Parkinson's disease (PD). Here, we design engineered extracellular vesicle-based nanoformulations (EVNs) address multiple factors for management PD. Specifically, EVN is developed coating CCR2-enriched mesenchymal stem cell-derived vesicles (MSC

Language: Английский

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Iron toxicity, ferroptosis and microbiota in Parkinson’s disease: Implications for novel targets

Advances in neurotoxicology, Journal Year: 2024, Volume and Issue: unknown, P. 105 - 132

Published: Jan. 1, 2024

Language: Английский

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Ghrelin Induces Ferroptosis Resistance and M2 Polarization of Microglia to Alleviate Neuroinflammation and Cognitive Impairment in Alzheimer’s Disease

Journal of Neuroimmune Pharmacology, Journal Year: 2025, Volume and Issue: 20(1)

Published: Jan. 11, 2025

Language: Английский

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Neuroinflammation and iron metabolism after intracerebral hemorrhage: a glial cell perspective

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

Published: Jan. 15, 2025

Intracerebral hemorrhage (ICH) is the most common subtype of hemorrhagic stroke causing significant morbidity and mortality. Previously clinical treatments for ICH have largely been based on a single pathophysiological perspective, there remains lack curative interventions. Following rupture cerebral blood vessels, metabolites activate resident immune cells such as microglia astrocytes, infiltrate peripheral cells, leading to release series inflammatory mediators. Degradation hemoglobin produces large amounts iron ions, an imbalance homeostasis production quantities harmful hydroxyl radicals. Neuroinflammation dysregulation brain metabolism are both important changes in ICH, can exacerbate secondary injury. There inseparable relationship between disorder activated glial after ICH. Glial participate through various mechanisms; meanwhile, accumulation exacerbates neuroinflammation by activating signaling pathways modulating functions so on. This review aims explore from perspective metabolism, linking complex changes, delving into exploration treatment approaches offering insights that could enhance management strategies.

Language: Английский

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