Focal degeneration of astrocytes in amyotrophic lateral sclerosis

Détails

ID Serval
serval:BIB_F31FC6B167F1
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Focal degeneration of astrocytes in amyotrophic lateral sclerosis
Périodique
Cell Death and Differentiation
Auteur⸱e⸱s
Rossi D., Brambilla L., Valori C. F., Roncoroni C., Crugnola A., Yokota T., Bredesen D. E., Volterra A.
ISSN
1350-9047
Statut éditorial
Publié
Date de publication
07/2008
Peer-reviewed
Oui
Volume
15
Numéro
11
Pages
1691-1700
Langue
anglais
Résumé
Astrocytes emerge as key players in motor neuron degeneration in Amyotrophic Lateral Sclerosis (ALS). Whether astrocytes cause direct damage by releasing toxic factors or contribute indirectly through the loss of physiological functions is unclear. Here we identify in the hSOD1(G93A) transgenic mouse model of ALS a degenerative process of the astrocytes, restricted to those directly surrounding spinal motor neurons. This phenomenon manifests with an early onset and becomes significant concomitant with the loss of motor cells and the appearance of clinical symptoms. Contrary to wild-type astrocytes, mutant hSOD1-expressing astrocytes are highly vulnerable to glutamate and undergo cell death mediated by the metabotropic type-5 receptor (mGluR5). Blocking mGluR5 in vivo slows down astrocytic degeneration, delays the onset of the disease and slightly extends survival in hSOD1(G93A) transgenic mice. We propose that excitotoxicity in ALS affects both motor neurons and astrocytes, favouring their local interactive degeneration. This new mechanistic hypothesis has implications for therapeutic interventions.Cell Death and Differentiation advance online publication, 11 July 2008; doi:10.1038/cdd.2008.99.
Mots-clé
amyotrophic lateral sclerosis, apoptosis, astrocyte, excitotoxicity, metabotropic glutamate receptor, Amyotrophic Lateral Sclerosis,pathology, Animals, Astrocytes,drug effects,enzymology,pathology, Caspase 3,metabolism, Cell Survival,drug effects, Cytoskeleton,drug effects,metabolism, Enzyme Activation,drug effects, Glial Fibrillary Acidic Protein,metabolism, Glutamates,pharmacology, Humans, Lumbar Vertebrae,enzymology, Mice, Motor Neurons,drug effects,enzymology,pathology, Mutant Proteins,metabolism, Pyridines,administration & dosage,pharmacology, Receptors, Metabotropic Glutamate,antagonists & inhibitors, Spheroids, Cellular,drug effects,enzymology,pathology, Superoxide Dismutase,metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
30/01/2009 10:13
Dernière modification de la notice
20/08/2019 16:20
Données d'usage