Involvement of Claudin-11 in Disruption of Blood-Brain, -Spinal Cord, and -Arachnoid Barriers in Multiple Sclerosis

Uchida, Yasuo; Sumiya, Tomohito; Tachikawa, Masanori; Yamakawa, Tetsu; Murata, Sho; Yagi, Yuta; Sato, Kenzo; Stephan, Alice; Ito, Katsuaki; Ohtsuki, Sumio; Couraud, Pierre Olivier; Suzuki, Takashi; Terasaki, Tetsuya

doi:10.1007/s12035-018-1207-5

Cited by 74 publications

(67 citation statements)

References 31 publications

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“…Huang et al (2017) showed similar alterations in BBB permeability, and claudin-5, occludin, and ZO-1 expression levels in cerebellar white matter could be prevented by a Kv1.3 channel blocker in EAE rats (Huang et al, 2017). Claudin-11 protein expression has also been shown to be significantly downregulated in MS patients and in EAE (Uchida et al, 2019). Differences in TJ alteration data between different groups may be due to differences in the specific EAE model, the time points examined, or the tissue in which the analysis was performed.…”

Section: Multiple Sclerosismentioning

confidence: 78%

“…Claudin-1 has been detected at the BBB at the messenger RNA (mRNA) level (Winkler et al, 2020); however, its expression at the BBB remains controversial in part due to possible antibody cross-reactivity between claudin-1 and claudin-3 (Bauer et al, 2014). Claudin-11 and claudin-12 have also been detected at the BBB, but claudin-12 is likely not important for barrier function (Castro Dias et al, 2019;Uchida et al, 2019).…”

Section: Molecular Composition and Regulation Of Tjs At The Bbbmentioning

confidence: 99%

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Structure, Function, and Regulation of the Blood-Brain Barrier Tight Junction in Central Nervous System Disorders

et al. 2020

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The blood-brain barrier (BBB) allows the brain to selectively import nutrients and energy critical to neuronal function while simultaneously excluding neurotoxic substances from the peripheral circulation. In contrast to the highly permeable vasculature present in most organs that reside outside of the central nervous system (CNS), the BBB exhibits a high transendothelial electrical resistance (TEER) along with a low rate of transcytosis and greatly restricted paracellular permeability. The property of low paracellular permeability is controlled by tight junction (TJ) protein complexes that seal the paracellular route between apposing brain microvascular endothelial cells. Although tight junction protein complexes are principal contributors to physical barrier properties, they are not static in nature. Rather, tight junction protein complexes are highly dynamic structures, where expression and/or localization of individual constituent proteins can be modified in response to pathophysiological stressors. These stressors induce modifications to tight junction protein complexes that involve de novo synthesis of new protein or discrete trafficking mechanisms. Such responsiveness of BBB tight junctions to diseases indicates that these protein complexes are critical for maintenance of CNS homeostasis. In fulfillment of this vital role, BBB tight junctions are also a major obstacle to therapeutic drug delivery to the brain. There is an opportunity to overcome this substantial obstacle and optimize neuropharmacology via acquisition of a detailed understanding of BBB tight junction structure, function, and regulation. In this review, we discuss physiological characteristics of tight junction protein complexes and how these properties regulate delivery of therapeutics to the CNS for treatment of neurological diseases. Specifically, we will discuss modulation of tight junction structure, function, and regulation both in the context of disease states and in the setting of pharmacotherapy. In particular, we will highlight how these properties can be potentially manipulated at the molecular level to increase CNS drug levels via paracellular transport to the brain.

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Section: Multiple Sclerosismentioning

confidence: 78%

Section: Molecular Composition and Regulation Of Tjs At The Bbbmentioning

confidence: 99%

Structure, Function, and Regulation of the Blood-Brain Barrier Tight Junction in Central Nervous System Disorders

et al. 2020

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“…50) Furthermore, the direct interaction of CD9 with a tight junctionrelated protein claudin-1 was demonstrated by means of a cross-linking proteomics study. 51) We have recently reported that claudin-5 and claudin-11 are expressed at the human and rodent BBB. 52) Although it is unclear whether CD9 interacts with claudin-5 or claudin-11 at the BBB, these results imply that reduced expression of CD9 may affect the integrity of endothelial cell-to-cell junctions.…”

Section: Discussionmentioning

confidence: 98%

Selective Protein Expression Changes of Leukocyte-Migration-Associated Cluster of Differentiation Antigens at the Blood–Brain Barrier in a Lipopolysaccharide-Induced Systemic Inflammation Mouse Model without Alteration of Transporters, Receptors or Tight Junction-Related Protein

Sato

Tachikawa

Watanabe

et al. 2019

Biological & Pharmaceutical Bulletin

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Leukocyte migration across the blood-brain barrier (BBB) is an important step in the progression of brain dysfunction in systemic inflammation. The purpose of this study was to identify the key regulatory molecule(s) at the BBB among the cluster of differentiation (CD) antigens involved in leucocyte migration in lipopolysaccharide (LPS)-induced systemic inflammation based on their absolute protein expressions. Here, we identified the absolute expression levels of 17 CD antigens in isolated brain capillaries (Bcap) of LPS-administered mice. Among them, the expression levels of CD54 and CD106 were dramatically increased in LPS-administered mice compared to the control by 6.21-and 3.67-fold, respectively. In peripheral blood mononuclear cells, the expression levels of CD11a/CD18, the counter-receptor for CD54, were similar to those of CD54 in Bcap of LPS-administered mice. On the other hand, the expression level of CD49d, part of CD29/ CD49d complex, which is the counter-receptor for CD106, was under the limit of quantification. It is thus likely that CD54 at the BBB is predominantly involved in promoting leukocyte migration across the BBB in systemic inflammation. The expression levels of CD9, CD49c and CD97, which are thought to be involved in cell-to-cell interaction, were decreased by 40-60% in Bcap of LPS-administered mice. In contrast, the expression levels of 9 transporters, 2 receptors, and 1 tight junction-related protein in Bcap of LPS-administered mice were essentially unchanged compared to the control. These results suggest that enhancement of leucocyte migration in systemic inflammation involves dynamic changes of CD antigens without alterations of other major functional molecules.

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“…While the importance of claudin-5 as a tight junction protein at the cerebral endothelium is widely recognized [59], the potential role of other claudins [60] is more contentious. Uchida et al [61] recently provided evidence in multiple sclerosis that claudin-11 is decreased at the BBB (and the blood-spinal cord and the blood-arachnoid barriers) contributing to barrier leakiness. In contrast, Castro Dias et al [62,63] found that loss of claudin-12 and claudin-3 had no effect on BBB permeability in mice and that claudin-3 was absent from the cerebral endothelium.…”

Section: Claudins At the Cerebral Endotheliummentioning

confidence: 99%

This was the year that was: brain barriers and brain fluid research in 2019

Keep

Jones²,

Drewes

2020

Fluids Barriers CNS

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This editorial highlights advances in brain barrier and brain fluid research published in 2019, as well as addressing current controversies and pressing needs. Topics include recent advances related to: the cerebral endothelium and the neurovascular unit; the choroid plexus, arachnoid membrane; cerebrospinal fluid and the glymphatic hypothesis; the impact of disease states on brain barriers and brain fluids; drug delivery to the brain; and translation of preclinical data to the clinic. This editorial also mourns the loss of two important figures in the field, Malcolm B. Segal and Edward G. Stopa.

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Involvement of Claudin-11 in Disruption of Blood-Brain, -Spinal Cord, and -Arachnoid Barriers in Multiple Sclerosis

Cited by 74 publications

References 31 publications

Structure, Function, and Regulation of the Blood-Brain Barrier Tight Junction in Central Nervous System Disorders

Structure, Function, and Regulation of the Blood-Brain Barrier Tight Junction in Central Nervous System Disorders

Selective Protein Expression Changes of Leukocyte-Migration-Associated Cluster of Differentiation Antigens at the Blood–Brain Barrier in a Lipopolysaccharide-Induced Systemic Inflammation Mouse Model without Alteration of Transporters, Receptors or Tight Junction-Related Protein

This was the year that was: brain barriers and brain fluid research in 2019

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