Calreticulin levels determine onset of early muscle denervation by fast motoneurons of ALS model mice.

Détails

ID Serval
serval:BIB_FC3AF9A33638
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Calreticulin levels determine onset of early muscle denervation by fast motoneurons of ALS model mice.
Périodique
Neurobiology of Disease
Auteur(s)
Bernard-Marissal N., Sunyach C., Marissal T., Raoul C., Pettmann B.
ISSN
1095-953X (Electronic)
ISSN-L
0969-9961
Statut éditorial
Publié
Date de publication
2015
Peer-reviewed
Oui
Volume
73
Pages
130-136
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Résumé
Although the precise signaling mechanisms underlying the vulnerability of some sub-populations of motoneurons in ALS remain unclear, critical factors such as metallo-proteinase 9 expression, neuronal activity and endoplasmic reticulum stress have been shown to be involved. In the context of SOD1(G93A) ALS mouse model, we previously showed that a two-fold decrease in calreticulin (CRT) is occurring in the vulnerable fast motoneurons. Here, we asked to which extent the decrease in CRT levels was causative to muscle denervation and/or motoneuron degeneration. Toward this goal, a hemizygous deletion of the crt gene in SOD1(G93A) mice was generated since the complete ablation of crt is embryonic lethal. We observed that SOD1(G93A);crt(+/-) mice display increased and earlier muscle weakness and muscle denervation compared to SOD1(G93A) mice. While CRT reduction in motoneurons leads to a strong upregulation of two factors important in motoneuron dysfunction, ER stress and mTOR activation, it does not aggravate motoneuron death. Our results underline a prevalent role for CRT levels in the early phase of muscle denervation and support CRT regulation as a potential therapeutic approach.
Pubmed
Web of science
Création de la notice
17/01/2015 11:04
Dernière modification de la notice
20/08/2019 16:27
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