Excitotoxicity-induced endocytosis mediates neuroprotection by TAT-peptide-linked JNK inhibitor.

Détails

ID Serval
serval:BIB_B36CE4901DE2
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Excitotoxicity-induced endocytosis mediates neuroprotection by TAT-peptide-linked JNK inhibitor.
Périodique
Journal of Neurochemistry
Auteur(s)
Vaslin A., Naegele-Tollardo S., Puyal J., Clarke P.G.
ISSN
1471-4159 (Electronic)
ISSN-L
0022-3042
Statut éditorial
Publié
Date de publication
2011
Volume
119
Numéro
6
Pages
1243-1252
Langue
anglais
Notes
Publication types: Journal Article
Résumé
ABSTRACT: Excitotoxicity and cerebral ischemia induce strong endocytosis in neurons, and we here investigate its functional role in neuroprotection by a functional transactivator of transcription (TAT)-peptide, the c-Jun N-terminal kinase (JNK) inhibitor D-JNKI1, against NMDA-excitotoxicity in vitro and neonatal ischemic stroke in P12 Sprague-Dawley rats. In both situations, the neuroprotective efficacy of D-JNKI1 was confirmed, but excessively high doses were counterproductive. Importantly, the induced endocytosis was necessary for neuroprotection, which required that the TAT-peptide be administered at a time when induced endocytosis was occurring. Uptake by other routes failed to protect, and even promoted cell death at high doses. Blocking the induced endocytosis of D-JNKI1 with heparin or with an excess of D-TAT-peptide eliminated the neuroprotection. We conclude that excitotoxicity-induced endocytosis is a basic property of stressed neurons that can target neuroprotective TAT-peptides into the neurons that need protection. Furthermore, it is the main mediator of neuroprotection by D-JNKI1. This may explain promising reports of strong neuroprotection by TAT-peptides without apparent side effects, and warns that the timing of peptide administration is crucial.
Pubmed
Web of science
Open Access
Oui
Création de la notice
12/01/2012 18:08
Dernière modification de la notice
20/08/2019 15:21
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