Targeting Cytokine-Mediated Inflammation in Brain Disorders: Developing New Treatment Strategies

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(1), P. 104 - 104

Published: Jan. 15, 2025

Cytokine-mediated inflammation is increasingly recognized for playing a vital role in the pathophysiology of wide range brain disorders, including neurodegenerative, psychiatric, and neurodevelopmental problems. Pro-inflammatory cytokines such as interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) cause neuroinflammation, alter function, accelerate disease development. Despite progress understanding these pathways, effective medicines targeting are still limited. Traditional anti-inflammatory immunomodulatory drugs peripheral inflammatory illnesses. Still, they face substantial hurdles when applied to central nervous system (CNS), blood-brain barrier (BBB) unwanted systemic effects. This review highlights developing treatment techniques modifying cytokine-driven focusing on advances that selectively target critical involved pathology. Novel approaches, cytokine-specific inhibitors, antibody-based therapeutics, gene- RNA-based interventions, sophisticated drug delivery systems like nanoparticles, show promise with respect lowering neuroinflammation greater specificity safety. Furthermore, developments biomarker discoveries neuroimaging improving our ability monitor responses, allowing more accurate personalized regimens. Preclinical clinical trial data demonstrate therapeutic potential tailored techniques. However, significant challenges remain, across BBB reducing off-target As research advances, creation personalized, cytokine-centered therapeutics has therapy landscape illnesses, giving patients hope better results higher quality life.

Language: Английский

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Emerging Role of Extracellular Vesicles as Biomarkers in Neurodegenerative Diseases and Their Clinical and Therapeutic Potential in Central Nervous System Pathologies

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(18), P. 10068 - 10068

Published: Sept. 19, 2024

The emerging role of extracellular vesicles (EVs) in central nervous system (CNS) diseases is gaining significant interest, particularly their applications as diagnostic biomarkers and therapeutic agents. EVs are involved intercellular communication secreted by all cell types. They contain specific markers a diverse cargo such proteins, lipids, nucleic acids, reflecting the physiological pathological state originating cells. Their reduced immunogenicity ability to cross blood-brain barrier make them promising candidates for both In context CNS diseases, have shown promise isolable from different body fluids, providing non-invasive method diagnosing monitoring disease progression. This makes useful early detection Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, where alterations content can be detected. Additionally, derived stem cells show potential promoting tissue regeneration repairing damaged tissues. An evaluation has been conducted on current clinical trials studying focusing application, treatment protocols, obtained results. review aims explore carriers highlighting advantages ongoing evaluating efficacy.

Language: Английский

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Small Extracellular Vesicles Promote Axon Outgrowth by Engaging the Wnt-Planar Cell Polarity Pathway

Cells, Journal Year: 2025, Volume and Issue: 14(1), P. 56 - 56

Published: Jan. 6, 2025

In neurons, the acquisition of a polarized morphology is achieved upon outgrowth single axon from one several neurites. Small extracellular vesicles (sEVs), such as exosomes, diverse sources are known to promote neurite and thus may have therapeutic potential. However, effect fibroblast-derived exosomes on elongation in neurons central nervous system under growth-permissive conditions remains unclear. Here, we show that sEVs neuronal mouse primary embryonic cortical neurons. Mechanistically, demonstrate sEV-induced increase requires endogenous Wnts core PCP components including Prickle, Vangl, Frizzled, Dishevelled. We internalized by colocalize with Wnt7b, induce relocalization Vangl2 distal during outgrowth. contrast, derived or astrocytes do not outgrowth, while activated inhibit elongation. Thus, our data reveal through Wnt-PCP pathway manner dependent Wnts.

Language: Английский

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Obesity and Adipose-Derived Extracellular Vesicles: Implications for Metabolic Regulation and Disease

Biomolecules, Journal Year: 2025, Volume and Issue: 15(2), P. 231 - 231

Published: Feb. 5, 2025

Obesity, a global epidemic, is major risk factor for chronic diseases such as type 2 diabetes, cardiovascular disorders, and metabolic syndrome. Adipose tissue, once viewed passive fat storage site, now recognized an active endocrine organ involved in regulation inflammation. In obesity, adipose tissue dysfunction disrupts balance, leading to insulin resistance increased production of adipose-derived extracellular vesicles (AdEVs). These play key role intercellular communication contribute dysregulation, affecting organs the heart, liver, brain. AdEVs carry bioactive molecules, including microRNAs, which influence inflammation, sensitivity, remodeling. system, can promote atherosclerosis vascular dysfunction, while those derived from brown offer cardioprotective effects. exacerbate complications diabetic cardiomyopathy cognitive decline. Additionally, are implicated liver diseases, fatty disease, by transferring inflammatory molecules lipotoxic microRNAs hepatocytes. findings highlight obesity-related disorders their promise therapeutic targets related diseases.

Language: Английский

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The Role of Complexity Theory in Understanding Brain's Neuron–Glia Interactions

European Journal of Neuroscience, Journal Year: 2025, Volume and Issue: 61(5)

Published: March 1, 2025

ABSTRACT Brain information processing complexity is conventionally recognized as derived from neuronal activity, with neurons and their dynamic signalling responsible for the transfer of information. However, brain also contains other non‐neuronal cells, glial which exceed number are involved in processes related coding by neural networks underlying functions. Decisive advances characterization molecular physiological properties cells shed light on active roles neurotransmission physiopathology. This expanded relationship between glia challenges traditional neurobiology highlighting reciprocal influence, where it difficult to determine whether or initiate drive interactions. interplay creates a dilemma, causal hierarchy these two cell types remains unresolved. A philosophical tool, ‘Theory Complexity’ Edgard Morin can help better explain study neuron–glia Morin's proposal useful transform knowledge, order review functions antireductionist pattern. In this manuscript, we will discuss how use ‘retroactive loop’ principle at level, proposing new philosophical‐experimental grid that neuroscientists understanding glia–neuron interactions brain.

Language: Английский

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Gasdermin-D Genetic Knockout Reduces Inflammasome-Induced Disruption of the Gut-Brain Axis After Traumatic Brain Injury

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(8), P. 3512 - 3512

Published: April 9, 2025

Traumatic brain injury (TBI) pathology is significantly mediated by an inflammatory response involving inflammasome activation, resulting in the release of interleukin (IL)-1β and pyroptotic cell death through gasdermin-D (GSDMD) cleavage. Inflammasome components are transported extracellular vesicles (EVs) to mediate systemic inflammation peripheral organs, including gut. The purpose this study was determine protective effect GSDMD knockout (KO) on TBI-induced EV signaling, gut function. GSDMD-KO C57BL6 (WT) mice were subjected controlled cortical impact model TBI. Cytokine expression assessed with electrochemiluminescent immunoassay immunoblotting cerebral cortex EVs examined for pathology-associated markers using flow cytometry, permeability determined. attenuated IL-1β IL-6 reduced IL-18 3 days post-injury. had decreased neuronal- gut-derived compared WT post-TBI. also different surface marker after These data demonstrate that ablation improves post-TBI pathology, suggesting may serve as a potential therapeutic target improvement TBI-associated pathologies.

Language: Английский

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hPSCs-derived brain organoids for disease modeling, toxicity testing and drug evaluation

Experimental Neurology, Journal Year: 2024, Volume and Issue: 385, P. 115110 - 115110

Published: Dec. 10, 2024

Language: Английский

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Unveiling the multifaceted roles of microRNAs in extracellular vesicles derived from mesenchymal stem cells: implications in tumor progression and therapeutic interventions

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

Published: Aug. 5, 2024

Mesenchymal stem/stromal cells (MSCs) have the capacity to migrate tumor sites

Language: Английский

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Distribution and Incorporation of Extracellular Vesicles into Chondrocytes and Synoviocytes

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 11942 - 11942

Published: Nov. 6, 2024

Osteoarthritis (OA) is a chronic disease affecting over 500 million people worldwide. As the population ages and obesity rates rise, societal burden of OA increasing. Pro-inflammatory cytokines, particularly interleukin-1β, are implicated in pathogenesis OA. Recent studies suggest that crosstalk between cartilage synovium contributes to development, but mechanisms remain unclear. Extracellular vesicles (EVs) were purified from cell culture-conditioned medium via ultracentrifugation confirmed using transmission electron microscopy, nanoparticle tracking analysis, western blotting. We demonstrated EVs taken up by human synoviocytes chondrocytes vitro, while vivo experiments revealed fluorescent-labelled injected into mouse joints incorporated synoviocytes. EV uptake was significantly inhibited dynamin-mediated endocytosis inhibitors, indicating plays major role this process. Additionally, co-culture with HEK-293 cells expressing red fluorescent protein (RFP)-tagged CD9 chondrocytic line OUMS-27 transfer RFP-positive across 600-nm not 30-nm filter. These findings released joint fluid within cartilage, potentially facilitating communication synovium. The results underscore importance pathophysiology.

Language: Английский

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Brain–Periphery Axes: The Potential Role of Extracellular Vesicles-Delivered miRNAs

Biology, Journal Year: 2024, Volume and Issue: 13(12), P. 1056 - 1056

Published: Dec. 16, 2024

Bidirectional communication between the central nervous system (CNS) and peripheral organs tissue has been widely documented in physiological pathological conditions. This relies on bilateral transmission of signaling molecules substances that circulate throughout body reach their target site(s) via blood other biological fluids (e.g., cerebrospinal fluid, lymph). One mechanisms by which these molecular messengers are exchanged is through secretion extracellular vesicles (EVs). EVs known to mediate cell-to-cell delivering molecules, including nucleic acids, proteins, lipids, various bioactive regulators. Moreover, can cross blood–brain barrier (BBB), enabling direct periphery brain. In particular, delivery microRNAs (miRNAs) modulate expression profiles recipient cells, thereby influencing functions. review synthesizes current findings about brain–periphery cross-talk mediated EVs-delivered miRNAs. Although this mechanism definitively shown a few cases, much evidence indirectly indicates it could brain–peripherical organs/tissue communication, especially Therefore, understanding process provide valuable insights for treatment management neurological systemic diseases.

Language: Английский

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