A 1-42-RAGE Interaction Disrupts Tight Junctions of the Blood-Brain Barrier Via Ca2+-Calcineurin Signaling

Kook, Sun Young; Hong, Hyun Seok; Moon, Minho; Ha, Chang Man; Chang, Sunghoe; Mook‐Jung, Inhee

doi:10.1523/jneurosci.6102-11.2012

Cited by 230 publications

(194 citation statements)

References 46 publications

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“…Irregular interendothelial junctions with fewer points of contact were also observed, with decreased TEER and increased paracellular permeability to fluorescein and albumin. TJ integrity in mouse endothelial cells was also regulated by ApoE [126], and A 1-42-RAGE interaction [127,128]. Some line of evidence also suggests that A -induced BBB permeability might be mediated by protein kinase C (PKC), a family of enzymes involved in transmembrane signal transduction.…”

Section: A -Induced Bbb Permeability and Transmigration Of Mononucleamentioning

confidence: 99%

“…A -endothelium interaction induces BBB permeability [125][126][127][128], possibly mediated by PKC inactivation [136]. A also increases adherence and transmigration of monocytes across the BBB [43, 137,138], mediated by the transcription factor NF-kB [140].…”

Section: A -Endothelium Interactionmentioning

confidence: 99%

“…BBB permeability is influenced by hypoxia/ischemia [21,25,[168][169][170]172], inflammation [19], oxidative stress [15], and A [125][126][127][128]. Astrocytes also contribute to BBB permeability during inflammation by releasing inflammatory cytokines [34,35], and amplify the endothelial response to ischemia by increasing junctional permeability [225].…”

Section: Bbb Permeabilitymentioning

confidence: 99%

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Vascular dysfunction in the pathogenesis of Alzheimer's disease — A review of endothelium-mediated mechanisms and ensuing vicious circles

Marco

Venneri

Farkas

et al. 2015

Neurobiology of Disease

232

185

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Article available under the terms of the CC-BY-NC-ND licence (https://creativecommons.org/licenses/by-nc-nd/4.0/) eprints@whiterose.ac.uk https://eprints.whiterose.ac.uk/ Reuse Unless indicated otherwise, fulltext items are protected by copyright with all rights reserved. The copyright exception in section 29 of the Copyright, Designs and Patents Act 1988 allows the making of a single copy solely for the purpose of non-commercial research or private study within the limits of fair dealing. The publisher or other rights-holder may allow further reproduction and re-use of this version -refer to the White Rose Research Online record for this item. Where records identify the publisher as the copyright holder, users can verify any specific terms of use on the publisher's website. TakedownIf you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing eprints@whiterose.ac.uk including the URL of the record and the reason for the withdrawal request.

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Section: A -Induced Bbb Permeability and Transmigration Of Mononucleamentioning

confidence: 99%

Section: A -Endothelium Interactionmentioning

confidence: 99%

Section: Bbb Permeabilitymentioning

confidence: 99%

See 1 more Smart Citation

Vascular dysfunction in the pathogenesis of Alzheimer's disease — A review of endothelium-mediated mechanisms and ensuing vicious circles

Marco

Venneri

Farkas

et al. 2015

Neurobiology of Disease

232

185

View full text Add to dashboard Cite

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“…At pathophysiological concentrations, amyloid-b forms neurotoxic oligomers and also selfaggregates, which leads to the development of cerebral b-amyloidosis and cerebral amyloid angiopathy. 79 More insight into the molecular mechanisms underlying amyloid-b-RAGE interaction-induced alterations in the BBB have been provided by Kook et al 113 They found that Ab1-42 induces enhanced permeability, disruption of zonula occludin-1 (ZO-1) expression in the plasma membrane and increased intracellular calcium and MMP secretion in cultured ECs in vitro, and disrupted microvessels near amyloid-b plaque-deposited areas, elevated RAGE expression and enhanced MMP secretion in microvessels of the brains of 5XFAD mice, an animal model for Alzheimer's disease. The BBB transport mechanisms for amyloid-b are displayed in Figure 5.…”

mentioning

confidence: 99%

Age-associated physiological and pathological changes at the blood–brain barrier: A review

Erdő

Dénès

Lange

2016

J Cereb Blood Flow Metab

351

260

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The age-associated decline of the neurological and cognitive functions becomes more and more serious challenge for the developed countries with the increasing number of aged populations. The morphological and biochemical changes in the aging brain are the subjects of many extended research projects worldwide for a long time. However, the crucial role of the blood-brain barrier (BBB) impairment and disruption in the pathological processes in age-associated neurodegenerative disorders received special attention just for a few years. This article gives an overview on the major elements of the blood-brain barrier and its supporting mechanisms and also on their alterations during development, physiological aging process and age-associated neurodegenerative disorders (Alzheimer's disease, multiple sclerosis, Parkinson's disease, pharmacoresistant epilepsy). Besides the morphological alterations of the cellular elements (endothelial cells, astrocytes, pericytes, microglia, neuronal elements) of the BBB and neurovascular unit, the changes of the barrier at molecular level (tight junction proteins, adheres junction proteins, membrane transporters, basal lamina, extracellular matrix) are also summarized. The recognition of new players and initiators of the process of neurodegeneration at the level of the BBB may offer new avenues for novel therapeutic approaches for the treatment of numerous chronic neurodegenerative disorders currently without effective medication. KeywordsAging, blood-brain barrier, endothelial cells, neurodegenerative disorders, transport systems Structure of the blood-brain barrier (BBB)Homeostasis of the extracellular microenvironment in the neural tissue of the brain as well as its protection against neurotoxic compounds and variations in the composition of the blood are important for normal function of the neurons. It is warranted by a structure formed between blood and brain, which is therefore called the BBB.1 Clear evidence for the existence of this permeability barrier in the brain emerged in 1909 with the demonstration by Edwin Goldman (a South African-German) that a dye injected into the blood stream of a rat stained the whole body -except for the brain and spinal cord. The opposite was also true: injection of the dye into the cerebral ventricles stained the brain and spinal cord but not the rest of the body. 2,3 This occurs because most organs of the body are perfused by capillaries lined with endothelial cells (ECs) that have small pores (fenestrations) to allow for the rapid movement of small molecules into the organ interstitial fluid from the circulation. However, the capillary endothelium of the brain and spinal cord lack these pores because the ECs of brain capillary are connected to each other by continuous tight junctions (TJs), produced by the interaction of several transmembrane proteins that project into and seal the paracellular pathway.3-5 The interaction of these junctional proteins effectively blocks the free diffusion of

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“…The latter two are of particular interest in the pathogenesis of Alzheimer's disease as they are involved in the cerebral homeostasis and clearance of Aβ [182]. In general, these receptors may provide targets for the brain directed delivery of drugs, which under normal circumstances do not cross the BBB, including large biopharmaceuticals.…”

Section: Cytotic Processes At the Bbbmentioning

confidence: 99%

The Blood–Brain Barrier: An Introduction to Its Structure and Function

Mahringer¹,

Ott²,

Fricker³

2013

Topics in Medicinal Chemistry

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The blood-brain barrier (BBB) formed by the brains microvascular system is impermeable for most therapeutically used compounds and overcoming this barrier remains to be one of the big challenges in modern medicine. It is composed of highly specialized endothelial cells, which are surrounded by pericytes and a basal membrane. Together with nearby astrocytes and neurons they constitute the so-called neurovascular unit, which restricts substance transfer from blood to brain and vice versa and maintains the cerebral ion homeostasis. Chapters of this book describe the discovery of the BBB, its evolutionary development as well as the cellular and molecular mechanisms, which underlay its structure and function in health and disease. The organization of tight junctional complexes or specific transport processes at the BBB will be addressed as well as methods to investigate BBB function in vitro and in vivo. Changes in the barrier function under several diseases conditions such as stroke or inflammation will be discussed as well as approaches to overcome the barrier by colloidal carriers or ultrasound.

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A 1-42-RAGE Interaction Disrupts Tight Junctions of the Blood-Brain Barrier Via Ca2+-Calcineurin Signaling

Cited by 230 publications

References 46 publications

Vascular dysfunction in the pathogenesis of Alzheimer's disease — A review of endothelium-mediated mechanisms and ensuing vicious circles

Vascular dysfunction in the pathogenesis of Alzheimer's disease — A review of endothelium-mediated mechanisms and ensuing vicious circles

Age-associated physiological and pathological changes at the blood–brain barrier: A review

The Blood–Brain Barrier: An Introduction to Its Structure and Function

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