The Crucial Role of the Blood–Brain Barrier in Neurodegenerative Diseases: Mechanisms of Disruption and Therapeutic Implications

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(2), P. 386 - 386

Published: Jan. 9, 2025

The blood-brain barrier (BBB) is a crucial structure that maintains brain homeostasis by regulating the entry of molecules and cells from bloodstream into central nervous system (CNS). Neurodegenerative diseases such as Alzheimer's Parkinson's disease, well ischemic stroke, compromise integrity BBB. This leads to increased permeability infiltration harmful substances, thereby accelerating neurodegeneration. In this review, we explore mechanisms underlying BBB disruption, including oxidative stress, neuroinflammation, vascular dysfunction, loss tight junction integrity, in patients with neurodegenerative diseases. We discuss how breakdown contributes neurotoxicity, abnormal accumulation pathological proteins, all which exacerbate neuronal damage facilitate disease progression. Furthermore, potential therapeutic strategies aimed at preserving or restoring function, anti-inflammatory treatments, antioxidant therapies, approaches enhance integrity. Given role neurodegeneration, maintaining its represents promising approach slow prevent progression

Language: Английский

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Role of Oxidative Stress in Blood–Brain Barrier Disruption and Neurodegenerative Diseases

Antioxidants, Journal Year: 2024, Volume and Issue: 13(12), P. 1462 - 1462

Published: Nov. 28, 2024

Upregulation of reactive oxygen species (ROS) levels is a principal feature observed in the brains neurodegenerative diseases such as Parkinson’s disease (PD) and Alzheimer’s (AD). In these diseases, oxidative stress can disrupt blood–brain barrier (BBB). This disruption allows neurotoxic plasma components, blood cells, pathogens to enter brain, leading increased ROS production, mitochondrial dysfunction, inflammation. Collectively, factors result protein modification, lipid peroxidation, DNA damage, and, ultimately, neural cell damage. this review article, we present mechanisms by which damage leads BBB breakdown brain diseases. Additionally, summarize potential therapeutic approaches aimed at reducing that contributes

Language: Английский

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Neurovascular unit, neuroinflammation and neurodegeneration markers in brain disorders

Frontiers in Cellular Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Oct. 25, 2024

Neurovascular unit (NVU) inflammation via activation of glial cells and neuronal damage plays a critical role in neurodegenerative diseases. Though the exact mechanism disease pathogenesis is not understood, certain biomarkers provide valuable insight into pathogenesis, severity, progression therapeutic efficacy. These markers can be used to assess pathophysiological status brain including neurons, astrocytes, microglia, oligodendrocytes, specialized microvascular endothelial cells, pericytes, NVU, blood-brain barrier (BBB) disruption. Damage or derangements tight junction (TJ), adherens (AdJ), gap (GJ) components BBB lead increased permeability neuroinflammation various disorders disorders. Thus, neuroinflammatory evaluated blood, cerebrospinal fluid (CSF), tissues determine neurological progression, responsiveness. Chronic common age-related Alzheimer's (AD), Parkinson's (PD), dementia. Neurotrauma/traumatic injury (TBI) also leads acute chronic responses. The expression some may altered many years even decades before onset In this review, we discuss neuroinflammation, neurodegeneration associated with disorders, especially those neurovascular pathologies. CSF, tissues. Neurofilament light (NfL), ubiquitin C-terminal hydrolase-L1 (UCHL1), fibrillary acidic protein (GFAP), Ionized calcium-binding adaptor molecule 1 (Iba-1), transmembrane 119 (TMEM119), aquaporin, endothelin-1, platelet-derived growth factor receptor beta (PDGFRβ) are important markers. Recent BBB-on-a-chip modeling offers promising potential for providing an in-depth understanding neurotherapeutics. Integration these clinical practice could potentially enhance early diagnosis, monitor improve outcomes.

Language: Английский

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Role of the transcription factor NRF2 in maintaining the integrity of the Blood-Brain Barrier

Fluids and Barriers of the CNS, Journal Year: 2024, Volume and Issue: 21(1)

Published: Nov. 21, 2024

The Blood-Brain Barrier (BBB) is a complex and dynamic interface that regulates the exchange of molecules cells between blood central nervous system. It undergoes structural functional throughout oxidative stress inflammation, which may compromise its integrity contribute to pathogenesis neurodegenerative diseases. Maintaining BBB utmost importance in preventing wide range neurological disorders. NRF2 main transcription factor cellular redox balance inflammation-related gene expression. has also demonstrated potential role regulating tight junction contributing inhibition ECM remodeling, by reducing expression several metalloprotease family members involved maintaining function. Overall, we review current insights on addressing protection against effects dysfunction, discuss involvement maintenance different neuropathological diseases, as well as, some activators have been used vitro vivo animal models for barrier dysfunction. Thus, emerging evidence suggests upregulation target genes could suppress stress, neuroinflammation, restore integrity, increase protection.

Language: Английский

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The role of microbiome in gut-brain-axis dysbiosis causing depression: From mechanisms to treatment

International review of neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Repetitive Low-Level Blast Exposure Alters Circulating Myeloperoxidase, Matrix Metalloproteinases, and Neurovascular Endothelial Molecules in Experienced Military Breachers

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 1808 - 1808

Published: Feb. 20, 2025

Repeated exposure to low-level blast overpressure, frequently experienced during explosive breaching and heavy weapons use in training operations, is increasingly recognised as a serious risk the neurological health of military personnel. Although research on underlying pathobiological mechanisms humans remains limited, this study investigated effects such circulating molecular biomarkers associated with inflammation, neurovascular damage, endothelial injury. Blood samples from breachers were analysed for myeloperoxidase (MPO), matrix metalloproteinases (MMPs), junctional proteins indicative blood-brain barrier (BBB) disruption including occludin (OCLN), zonula occludens-1 (ZO-1), aquaporin-4 (AQP4), syndecan-1 (SD-1). The results revealed significantly elevated levels MPO, MMP-3, MMP-9, MMP-10 compared unexposed controls, suggesting heightened oxidative stress, vascular Increased OCLN SD-1 further indicated BBB glycocalyx degradation breachers. These findings highlight potential chronic unit damage/dysfunction repeated underscore importance early targeted interventions-such reducing reinforcing integrity, managing inflammation-that could be essential mitigating long-term impairment exposure.

Language: Английский

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Role of tight junction proteins in shaping the immune milieu of malignancies

Expert Review of Clinical Immunology, Journal Year: 2024, Volume and Issue: 20(11), P. 1305 - 1321

Published: Aug. 10, 2024

Introduction Tight junctions (TJs) and their constituent proteins play pivotal roles in cellular physiology anatomy by establishing functional boundaries within between neighboring cells. While the involvement of TJ proteins, such as claudins, cancer is extensively studied, studies highlighting interaction with immune system are still meager. Studies indicate that alterations cytokines cell populations can affect compromising barrier function exacerbating pro-inflammatory conditions, potentially leading to epithelial malignancy. Disrupted TJs established tumors may foster a pro-tumor microenvironment, facilitating tumor progression, invasion, epithelial-to-mesenchymal transition metastasis. Although previous literature contains many describing pathogenesis malignancies role modulating microenvironment just beginning be unleashed.

Language: Английский

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Secretome of brain microvascular endothelial cells promotes endothelial barrier tightness and protects against hypoxia-induced vascular leakage

Molecular Medicine, Journal Year: 2024, Volume and Issue: 30(1)

Published: Aug. 26, 2024

Abstract Cell-based therapeutic strategies have been proposed as an alternative for brain and blood vessels repair after stroke, but their clinical application is hampered by potential adverse effects. We therefore tested the hypothesis that secretome of these cells might be used instead to still focus on cell-based strategies. characterized composition effect microvascular endothelial (BMECs) primary in vitro human models angiogenesis vascular barrier. Two different batches produced high scale (scHSP) were analysed mass spectrometry. Human CD34 + -derived (CD34 -ECs) well EC monolayer (CMECs) blood–brain barrier (BBB). Cells also exposed oxygen–glucose deprivation (OGD) conditions treated with scHSP during reoxygenation. Protein yield showed good reproducibility. increased -EC proliferation, tubulogenesis, migration. Proteomic analysis revealed presence growth factors proteins modulating cell metabolism inflammatory pathways. improved integrity CMECs, upregulated expression junctional proteins. Such effects mediated through activation interferon pathway downregulation Wnt signalling. Furthermore, OGD altered permeability both CMECs BBB, while prevented OGD-induced leakage models. These upregulation regulation MAPK/VEGFR2. Finally, our results highlight possibility using from BMECs a promote protect ischemia-induced leakage.

Language: Английский

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Special Issue “The Tight Junction and Its Proteins: From Structure to Pathologies”

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(23), P. 13154 - 13154

Published: Dec. 7, 2024

Most tight junction (TJ) proteins build epithelial and endothelial barriers [...].

Language: Английский

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Investigation into the Potential Mechanism of Radix Paeoniae Rubra Against Ischemic Stroke Based on Network Pharmacology

Nutrients, Journal Year: 2024, Volume and Issue: 16(24), P. 4409 - 4409

Published: Dec. 23, 2024

Radix Paeoniae Rubra (RPR), an edible and medicinal Traditional Chinese Medicine (TCM), is extensively employed in therapeutic interventions of cardiovascular cerebrovascular diseases. However, the curative effect RPR on ischemic stroke remains ambiguous. This work integrated network pharmacology, molecular docking, experimental validation to explore mechanisms treating stroke. In this study, we preliminarily elucidated mechanism through docking analysis, verification. The results indicated that improved neurological deficit scores, decreased size infarcts, reduced brain edema symptoms tMCAO mice model. Furthermore, pharmacology four core targets (MAPK3, TNF-α, MAPK14, JNK) closely related RPR's treatment were identified, exhibiting strong affinity with two key active components RPR: albiflorin (AF) β-sitosterol (BSS). Western blot showed potential for by regulating MAPK signaling pathway. Moreover, its main ingredients exhibited a significant inhibitory platelets. conclusion, study revealed alleviates injury activating pathway, protective may partly stem from inhibiting platelet activation. provide scientific basis development utilization as natural material prevent anti-platelet therapy.

Language: Английский

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