The impact of neuroinflammation on neuronal integrity

Immunological Reviews, Journal Year: 2024, Volume and Issue: 327(1), P. 8 - 32

Published: Oct. 1, 2024

Neuroinflammation, characterized by a complex interplay among innate and adaptive immune responses within the central nervous system (CNS), is crucial in responding to infections, injuries, disease pathologies. However, dysregulation of neuroinflammatory response could significantly affect neurons terms function structure, leading profound health implications. Although tremendous progress has been made understanding relationship between processes alterations neuronal integrity, specific implications concerning both structure have not extensively covered, with exception perspectives on glial activation neurodegeneration. Thus, this review aims provide comprehensive overview multifaceted interactions key inflammatory players, exploring mechanisms through which inflammation influences functionality structural integrity CNS. Further, it will discuss how these lead impairment functions architecture highlight consequences caused dysregulated functions, such as cognitive dysfunction mood disorders. By integrating insights from recent research findings, enhance our landscape set stage for future interventions that transform current approaches preserve CNS-related conditions.

Language: Английский

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What Are the Functions of Caveolins and Their Role in Neurologic Disorders?

Neurology, Journal Year: 2025, Volume and Issue: 104(3)

Published: Jan. 13, 2025

Language: Английский

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Animal Models of Non-Respiratory, Post-Acute Sequelae of COVID-19

Viruses, Journal Year: 2025, Volume and Issue: 17(1), P. 98 - 98

Published: Jan. 14, 2025

Post-acute sequelae of COVID-19 (PASC) are a diverse set symptoms and syndromes driven by dysfunction multiple organ systems that can persist for years negatively impact the quality life millions individuals. We currently lack specific therapeutics patients with PASC, due in part to an incomplete understanding its pathogenesis, especially non-pulmonary sequelae. Here, we discuss three animal models have been utilized investigate PASC: non-human primates (NHPs), hamsters, mice. focus on neurological, gastrointestinal, cardiovascular PASC highlight advances mechanistic insight made using these models, as well discussing warrant continued intensive research.

Language: Английский

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A Brain Endothelial Cell Caveolin-1/CXCL10 Axis Promotes T Cell Transcellular Migration Across the Blood-Brain Barrier

ASN NEURO, Journal Year: 2025, Volume and Issue: 17(1)

Published: March 10, 2025

The mechanisms that govern whether T cells cross blood-brain barrier (BBB) endothelium by transcellular versus paracellular routes are unclear. Caveolin-1 is a membrane scaffolding and signaling protein associated with transmigration through the endothelial cytoplasm. Here, we report neuroinflammatory chemokine CXCL10 induced transcellular, caveolar of CXCR3+ CD4+ cells. Specifically, data revealed CXCL10-induced requires expression ICAM-1 in brain receptor, CXCR3, LFA-1 Moreover, promoted aggregation into cytoplasmic stores, providing mechanism for activation recruitment to migrate at locations, distal cell-cell junctions. Consistent our vitro data, genetic ablation reduces infiltration CNS experimental autoimmune encephalomyelitis. Our findings establish novel which utilize dependent intracellular stores license migration across barrier.

Language: Английский

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TRPV4 in cerebral small vessel disease: A key interacting partner

Vascular Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 107492 - 107492

Published: March 1, 2025

Cerebral small vessel disease (cSVD) is a major cause of vascular cognitive impairment and dementia. The underlying mechanisms are centered around the dysfunction neurovascular unit include an blood-brain barrier (BBB) permeability, decreased cerebrovascular reactivity cerebral hypoperfusion. cells composing express wide variety mechanosensitive ion channels that relevant for these processes. Recent research has increasingly focused on mechanobiology microvessels with recent evidence pointing towards significant role transient receptor potential vanilloid 4 (TRPV4). This Ca2+-permeable channel regulates key physiological functions, including tone, angiogenesis, BBB integrity neuroinflammation. Beyond its role, implicates TRPV4 in pathological processes such as remodelling, impaired reactivity, dysfunction. In this review, we explore multiple roles within unit, interactions molecular partners, discuss contribution to cSVD.

Language: Английский

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Caveolae-Mediated Transcytosis and Its Role in Neurological Disorders

Biomolecules, Journal Year: 2025, Volume and Issue: 15(4), P. 456 - 456

Published: March 21, 2025

The blood-brain barrier (BBB) controls the flow of substances to maintain a homeostatic environment in brain, which is highly regulated and crucial for normal function central nervous system (CNS). Brain endothelial cells (bECs), are directly exposed blood, play most important role maintaining integrity BBB. Unlike other tissues, bECs have two unique features: specialized tight junctions actively suppressed transcellular vesicle trafficking (transcytosis). These features help relatively low permeability CNS barrier. In addition predominant BBB, caveolae-mediated adsorptive transcytosis has attracted much interest recent years. active suppression dynamically during development response diseases. Altered been reported several neurological diseases, but understanding this process limited. Here, we review based on previous studies discuss its breakdown BBB disorders.

Language: Английский

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Caveolae: Metabolic Platforms at the Crossroads of Health and Disease

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 2918 - 2918

Published: March 24, 2025

Caveolae are small flask-shaped invaginations of the plasma membrane enriched in cholesterol and sphingolipids. They play a critical role various cellular processes, including signal transduction, endocytosis, mechanotransduction. Caveolin proteins, specifically Cav-1, Cav-2, Cav-3, addition to their as structural components caveolae, have been found regulate activity signaling molecules. A growing body research has highlighted pivotal caveolae caveolins maintaining metabolic homeostasis. Indeed, studies demonstrated that interact with key insulin signaling, glucose uptake, lipid metabolism, thereby influencing energy production storage. The dysfunction or altered expression associated disorders, obesity, type 2 diabetes, ocular diseases. Remarkably, mutations caveolin genes can disrupt balance, promote oxidative stress, exacerbate dysregulation. This review examines current on molecular mechanisms through which explores involvement pathogenesis discusses potential therapeutic strategies targeting function stabilization restore

Language: Английский

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Translating animal models of SARS-CoV-2 infection to vascular, neurological and gastrointestinal manifestations of COVID-19

Disease Models & Mechanisms, Journal Year: 2025, Volume and Issue: 18(9)

Published: April 8, 2025

ABSTRACT Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) initiated a global pandemic resulting in an estimated 775 million infections with over 7 deaths, it has become evident that COVID-19 is not solely pulmonary disease. Emerging evidence shown that, subset patients, certain symptoms − including chest pain, stroke, anosmia, dysgeusia, diarrhea and abdominal pain – all indicate role vascular, neurological gastrointestinal (GI) pathology disease process. Many these processes persist long after been resolved, ‘long COVID’ or post-acute sequelae (PASC). The molecular mechanisms underlying systemic conditions associated remain incompletely defined. Appropriate animal models provide method understanding at system level through study progression, tissue pathology, immune response to pathogen behavioral responses. However, very few studies have addressed PASC whether existing hold promise for studying this challenging problem. Here, we review current literature on cardiovascular, GI pathobiology caused by along established manifestations their prospects use studies. Our aim guidance selection appropriate order recapitulate aspects enhance translatability mechanistic

Language: Английский

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An integrated bioinformatics approach reveals the potential role of microRNA-30b-5p and let-7a-5p during SARS CoV-2 spike-1 mediated neuroinflammation

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 277, P. 134329 - 134329

Published: Aug. 7, 2024

SARS-CoV-2 induced neuroinflammation contributing to neurological sequelae is one of the critical outcomes long-COVID, however underlying regulatory mechanisms involved therein are poorly understood. We deciphered profile dysregulated microRNAs, their targets, associated pathways, protein-protein interactions (PPI), transcription factor-hub genes interaction networks, hub genes-microRNA co-regulatory networks in Spike-1 (S1) stimulated microglial cells along with candidate drug prediction using RNA-sequencing and multiple bioinformatics approaches. identified 11 microRNAs S1-stimulated (p < 0.05). KEGG analysis revealed involvement important neuroinflammatory pathways such as MAPK signalling, PI3K-AKT Ras signalling axon guidance. PPI further these pathways. Real time PCR validation confirmed a significant upregulation microRNA-30b-5p let-7a-5p; proinflammatory cytokines- IL-6, TNF-α, IL-1β, GM-CSF; inflammatory genes- PIK3CA AKT cells, while PTEN SHIP1 expression was decreased compared non-stimulated cells. Drug indicated resveratrol, diclofenac rapamycin potential drugs based on degree genes. Thus, targeting and/or intermediate molecules would be prospective immunotherapeutic approach alleviating SARS-CoV-2-S1 mediated neuroinflammation; needs investigations.

Language: Английский

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