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

Details

Ressource 1Download: BIB_12563898F2FA.P001.pdf (2325.25 [Ko])
State: Public
Version: author
Serval ID
serval:BIB_12563898F2FA
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
c-Jun N-terminal kinase has a key role in Alzheimer disease synaptic dysfunction in vivo.
Journal
Cell Death and Disease
Author(s)
Sclip A., Tozzi A., Abaza A., Cardinetti D., Colombo I., Calabresi P., Salmona M., Welker E., Borsello T.
ISSN
2041-4889 (Electronic)
Publication state
Published
Issued date
2014
Peer-reviewed
Oui
Volume
5
Pages
e1019
Language
english
Notes
Publication types: Journal Article Publication Status: epublish
Abstract
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
Yes
Create date
30/01/2014 8:44
Last modification date
20/08/2019 12:40
Usage data