Targeting neonatal ischemic brain injury with a pentapeptide-based irreversible caspase inhibitor View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-09

AUTHORS

D Chauvier, S Renolleau, S Holifanjaniaina, S Ankri, M Bezault, L Schwendimann, C Rousset, R Casimir, J Hoebeke, M Smirnova, G Debret, A-P Trichet, Y Carlsson, X Wang, E Bernard, M Hébert, J-M Rauzier, S Matecki, A Lacampagne, P Rustin, J Mariani, H Hagberg, P Gressens, C Charriaut-Marlangue, E Jacotot

ABSTRACT

Brain protection of the newborn remains a challenging priority and represents a totally unmet medical need. Pharmacological inhibition of caspases appears as a promising strategy for neuroprotection. In a translational perspective, we have developed a pentapeptide-based group II caspase inhibitor, TRP601/ORPHA133563, which reaches the brain, and inhibits caspases activation, mitochondrial release of cytochrome c, and apoptosis in vivo. Single administration of TRP601 protects newborn rodent brain against excitotoxicity, hypoxia-ischemia, and perinatal arterial stroke with a 6-h therapeutic time window, and has no adverse effects on physiological parameters. Safety pharmacology investigations, and toxicology studies in rodent and canine neonates, suggest that TRP601 is a lead compound for further drug development to treat ischemic brain damage in human newborns. More... »

PAGES

e203

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/cddis.2011.87

DOI

http://dx.doi.org/10.1038/cddis.2011.87

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1007711679

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/21881605


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