Status: Bibliographieeintrag
Standort: ---
Exemplare:
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| Online-Ressource |
Verfasst von: | Neuhaus, Winfried [VerfasserIn]  |
| Mahringer, Anne [VerfasserIn]  |
Titel: | Reversible opening of the blood-brain barrier by claudin-5-binding variants of Clostridium perfringens enterotoxin's claudin-binding domain |
Verf.angabe: | Winfried Neuhaus, Anna Piontek, Jonas Protze, Miriam Eichner, Anne Mahringer, Eva-Anne Subileau, In-Fah M. Lee, Jörg D. Schulzke, Gerd Krause, Jörg Piontek |
E-Jahr: | 2018 |
Jahr: | 2 February 2018 |
Umfang: | 15 S. |
Fussnoten: | Gesehen am 19.02.2020 |
Titel Quelle: | Enthalten in: Biomaterials |
Ort Quelle: | Amsterdam [u.a.] : Elsevier Science, 1980 |
Jahr Quelle: | 2018 |
Band/Heft Quelle: | 161(2018), Seite 129-143 |
ISSN Quelle: | 0142-9612 |
Abstract: | The blood-brain barrier (BBB) prevents entry of neurotoxic substances but also that of drugs into the brain. Here, the paracellular barrier is formed by tight junctions (TJs) with claudin-5 (Cldn5) being the main sealing constituent. Transient BBB opening by targeting Cldn5 could improve paracellular drug delivery. The non-toxic C-terminal domain of Clostridium perfringens enterotoxin (cCPE) binds to a subset of claudins, e.g., Cldn3, -4. Structure-based mutagenesis was used to generate Cldn5-binding variants (cCPE-Y306W/S313H and cCPE-N218Q/Y306W/S313H). These cCPE-variants were tested for transient TJ opening using multiple in vitro BBB models: Primary porcine brain endothelial cells, coculture of primary rat brain endothelial cells with astrocytes and mouse cerebEND cells. cCPE-Y306W/S313H and cCPE-N218Q/Y306W/S313H but neither cCPE-wt nor cCPE-Y306A/L315A (not binding to claudins) decreased transendothelial electrical resistance in a concentration-dependent and reversible manner. Furthermore, permeability of carboxyfluorescein (with size of CNS drugs) was increased. cCPE-Y306W/S313H but neither cCPE-wt nor cCPE-Y306A/L315A bound to Cldn5-expressing brain endothelial cells. However, freeze-fracture EM showed that cCPE-Y306W/S313H did not cause drastic TJ breakdown. In sum, Cldn5-binding cCPE-variants enabled mild and transient opening of brain endothelial TJs. Using reliable in vitro BBB models, the results demonstrate that cCPE-based biologics designed to bind Cldn5 improve paracellular drug delivery across the BBB. |
DOI: | doi:10.1016/j.biomaterials.2018.01.028 |
URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: https://doi.org/10.1016/j.biomaterials.2018.01.028 |
| Volltext: http://www.sciencedirect.com/science/article/pii/S0142961218300425 |
| DOI: https://doi.org/10.1016/j.biomaterials.2018.01.028 |
Datenträger: | Online-Ressource |
Sprache: | eng |
Sach-SW: | Blood brain barrier |
| Claudin |
| enterotoxin |
| Paracellular drug delivery |
| Tight junction |
K10plus-PPN: | 169038638X |
Verknüpfungen: | → Zeitschrift |
Reversible opening of the blood-brain barrier by claudin-5-binding variants of Clostridium perfringens enterotoxin's claudin-binding domain / Neuhaus, Winfried [VerfasserIn]; 2 February 2018 (Online-Ressource)
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