Cardiac glycosides target barrier inflammation of the vasculature, meninges and choroid plexus.

Anti-Inflammatory Agents / pharmacology Blood-Brain Barrier / drug effects Cells, Cultured Choroid Plexus / drug effects Digoxin / pharmacology Drug Evaluation, Preclinical Endothelial Cells / drug effects High-Throughput Screening Assays Humans Inflammation / drug therapy Inflammation Mediators / metabolism Lanatosides / pharmacology Meninges / drug effects Pericytes / drug effects Tissue Culture Techniques

Journal

Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179

Informations de publication

Date de publication:
26 02 2021
Historique:
received: 01 08 2020
accepted: 03 02 2021
entrez: 27 2 2021
pubmed: 28 2 2021
medline: 10 8 2021
Statut: epublish

Résumé

Neuroinflammation is a key component of virtually all neurodegenerative diseases, preceding neuronal loss and associating directly with cognitive impairment. Neuroinflammatory signals can originate and be amplified at barrier tissues such as brain vasculature, surrounding meninges and the choroid plexus. We designed a high content screening system to target inflammation in human brain-derived cells of the blood-brain barrier (pericytes and endothelial cells) to identify inflammatory modifiers. Screening an FDA-approved drug library we identify digoxin and lanatoside C, members of the cardiac glycoside family, as inflammatory-modulating drugs that work in blood-brain barrier cells. An ex vivo assay of leptomeningeal and choroid plexus explants confirm that these drugs maintain their function in 3D cultures of brain border tissues. These results suggest that cardiac glycosides may be useful in targeting inflammation at border regions of the brain and offer new options for drug discovery approaches for neuroinflammatory driven degeneration.

Identifiants

DOI: 10.1038/s42003-021-01787-x PMID: 33637884 PMC: PMC7910294
pubmed: 33637884
doi: 10.1038/s42003-021-01787-x
pii: 10.1038/s42003-021-01787-x
pmc: PMC7910294
doi:

Substances chimiques

Anti-Inflammatory Agents 0
Inflammation Mediators 0
Lanatosides 0
lanatoside C 5RR3JFZ771
Digoxin 73K4184T59

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

260

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Auteurs

Deidre Jansson (D)

Department of Pharmacology and Clinical Pharmacology, The University of Auckland, Auckland, New Zealand.
Centre for Brain Research, The University of Auckland, Auckland, New Zealand.
Department of Psychiatry and Behavioural Science, University of Washington, Seattle, WA, USA.
ORCID: 0000-0001-9757-8682

Victor Birger Dieriks (VB)

Centre for Brain Research, The University of Auckland, Auckland, New Zealand.
Department of Anatomy and Medical Imaging, The University of Auckland, Auckland, New Zealand.
ORCID: 0000-0002-9392-3327

Justin Rustenhoven (J)

Center for Brain Immunology and Glia (BIG), Washington University, St. Louis, MO, USA.
Department of Pathology and Immunology, School of Medicine, Washington University in St Louis, St. Louis, MO, USA.

Leon C D Smyth (LCD)

Department of Pathology, University of Otago, Christchurch, New Zealand.
Centre for Free Radical Research, University of Otago, Christchurch, New Zealand.

Emma Scotter (E)

Department of Pharmacology and Clinical Pharmacology, The University of Auckland, Auckland, New Zealand.
Centre for Brain Research, The University of Auckland, Auckland, New Zealand.
ORCID: 0000-0003-4064-3599

Miranda Aalderink (M)

Department of Pharmacology and Clinical Pharmacology, The University of Auckland, Auckland, New Zealand.
Centre for Brain Research, The University of Auckland, Auckland, New Zealand.

Sheryl Feng (S)

Department of Pharmacology and Clinical Pharmacology, The University of Auckland, Auckland, New Zealand.
Centre for Brain Research, The University of Auckland, Auckland, New Zealand.

Rebecca Johnson (R)

Department of Pharmacology and Clinical Pharmacology, The University of Auckland, Auckland, New Zealand.
Centre for Brain Research, The University of Auckland, Auckland, New Zealand.

Patrick Schweder (P)

Department of Neurosurgery, Auckland City Hospital, Auckland, New Zealand.

Edward Mee (E)

Department of Neurosurgery, Auckland City Hospital, Auckland, New Zealand.

Peter Heppner (P)

Starship Hospital, Auckland, New Zealand.

Clinton Turner (C)

Department of Anatomical Pathology, LabPlus, Auckland City Hospital, Auckland, New Zealand.

Maurice Curtis (M)

Centre for Brain Research, The University of Auckland, Auckland, New Zealand.
Department of Anatomy and Medical Imaging, The University of Auckland, Auckland, New Zealand.

Richard Faull (R)

Centre for Brain Research, The University of Auckland, Auckland, New Zealand.
Department of Anatomy and Medical Imaging, The University of Auckland, Auckland, New Zealand.

Mike Dragunow (M)

Department of Pharmacology and Clinical Pharmacology, The University of Auckland, Auckland, New Zealand. m.dragunow@auckland.ac.nz.
Centre for Brain Research, The University of Auckland, Auckland, New Zealand. m.dragunow@auckland.ac.nz.
ORCID: 0000-0003-1711-1631

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Classifications MeSH

questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Anti-inflammatoires › Cardiac glycosides target barrier inflammation...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Barrière hémato-encéphalique › Cardiac glycosides target barrier inflammation...
questionsmedicales.fr › Cellules › Cellules cultivées › Cardiac glycosides target barrier inflammation...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Ventricules cérébraux › Plexus choroïde › Cardiac glycosides target barrier inflammation...
questionsmedicales.fr › Glucides › Hétérosides › Glucosides cardiotoniques › Glucosides digitaliques › Digoxine › Cardiac glycosides target barrier inflammation...
questionsmedicales.fr › Techniques d'investigation › Évaluation préclinique de médicament › Cardiac glycosides target barrier inflammation...
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules endothéliales › Cardiac glycosides target barrier inflammation...
questionsmedicales.fr › Techniques d'investigation › Tests de criblage à haut débit › Cardiac glycosides target barrier inflammation...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Cardiac glycosides target barrier inflammation...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Inflammation › Cardiac glycosides target barrier inflammation...
questionsmedicales.fr › Facteurs biologiques › Médiateurs de l'inflammation › Cardiac glycosides target barrier inflammation...
questionsmedicales.fr › Glucides › Hétérosides › Glucosides cardiotoniques › Glucosides digitaliques › Lanatoside › Cardiac glycosides target barrier inflammation...
questionsmedicales.fr › Système nerveux › Système nerveux central › Méninges › Cardiac glycosides target barrier inflammation...
questionsmedicales.fr › Structures de l'embryon › Feuillets embryonnaires › Mésoderme › Péricytes › Cardiac glycosides target barrier inflammation...
questionsmedicales.fr › Techniques d'investigation › Techniques in vitro › Techniques de culture › Techniques de culture de tissus › Cardiac glycosides target barrier inflammation...