c-Jun N-terminal kinase has a key role in Alzheimer disease synaptic dysfunction in vivo.

Détails

Ressource 1Télécharger: BIB_12563898F2FA.P001.pdf (2325.25 [Ko])
Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_12563898F2FA
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
c-Jun N-terminal kinase has a key role in Alzheimer disease synaptic dysfunction in vivo.
Périodique
Cell Death and Disease
Auteur(s)
Sclip A., Tozzi A., Abaza A., Cardinetti D., Colombo I., Calabresi P., Salmona M., Welker E., Borsello T.
ISSN
2041-4889 (Electronic)
Statut éditorial
Publié
Date de publication
2014
Peer-reviewed
Oui
Volume
5
Pages
e1019
Langue
anglais
Notes
Publication types: Journal Article Publication Status: epublish
Résumé
Altered synaptic function is considered one of the first features of Alzheimer disease (AD). Currently, no treatment is available to prevent the dysfunction of excitatory synapses in AD. Identification of the key modulators of synaptopathy is of particular significance in the treatment of AD. We here characterized the pathways leading to synaptopathy in TgCRND8 mice and showed that c-Jun N-terminal kinase (JNK) is activated at the spine prior to the onset of cognitive impairment. The specific inhibition of JNK, with its specific inhibiting peptide D-JNKI1, prevented synaptic dysfunction in TgCRND8 mice. D-JNKI1 avoided both the loss of postsynaptic proteins and glutamate receptors from the postsynaptic density and the reduction in size of excitatory synapses, reverting their dysfunction. This set of data reveals that JNK is a key signaling pathway in AD synaptic injury and that its specific inhibition offers an innovative therapeutic strategy to prevent spine degeneration in AD.
Pubmed
Web of science
Open Access
Oui
Création de la notice
30/01/2014 9:44
Dernière modification de la notice
20/08/2019 13:40
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