UnissResearch

Logo Universitàegli studi di Sassari
titoli, abstracts, parole chiave >>>
Astroglial inhibition of NF-κB does not ameliorate disease onset and progression in a mouse model for Amyotrophic Lateral Sclerosis (ALS)

Crosio, Claudia and Valle, Cristiana and Casciati, Arianna and Iaccarino, Ciro and Carrì, Maria Teresa (2011) Astroglial inhibition of NF-κB does not ameliorate disease onset and progression in a mouse model for Amyotrophic Lateral Sclerosis (ALS). PLoS One, Vol. 6 (3), e17187. ISSN 1932-6203. Article.

[img]
Preview
Full text disponibile come PDF Richiede visualizzatore di PDF come GSview, Xpdf o Adobe Acrobat Reader
Available under License Creative Commons Attribution.

2098Kb

DOI: 10.1371/journal.pone.0017187

Abstract

Motor neuron death in amyotrophic lateral sclerosis (ALS) is considered a “non-cell autonomous” process, with astrocytes playing a critical role in disease progression. Glial cells are activated early in transgenic mice expressing mutant SOD1, suggesting that neuroinflammation has a relevant role in the cascade of events that trigger the death of motor neurons. An inflammatory cascade including COX2 expression, secretion of cytokines and release of NO from astrocytes may descend from activation of a NF-κB-mediated pathway observed in astrocytes from ALS patients and in experimental models. We have attempted rescue of transgenic mutant SOD1 mice through the inhibition of the NF-κB pathway selectively in astrocytes. Here we show that despite efficient inhibition of this major pathway, double transgenic mice expressing the mutant SOD1G93A ubiquitously and the dominant negative form of IκBα (IκBαAA) in astrocytes under control of the GFAP promoter show no benefit in terms of onset and progression of disease. Our data indicate that motor neuron death in ALS cannot be prevented by inhibition of a single inflammatory pathway because alternative pathways are activated in the presence of a persistent toxic stimulus.

Item Type:Article
ID Code:5786
Status:Published
Refereed:Yes
Uncontrolled Keywords:Motor neuron disease, Amyotrophic Lateral Sclerosis (ALS), NF-kB activity
Subjects:Area 05 - Scienze biologiche > BIO/11 Biologia molecolare
Divisions:001 Università di Sassari > 01 Dipartimenti > Scienze fisiologiche, biochimiche e cellulari
Publisher:Public Library of Science
ISSN:1932-6203
Copyright Holders:© 2011 Crosio et al.
Deposited On:22 Mar 2011 10:41

I documenti depositati in UnissResearch sono protetti dalle leggi che regolano il diritto d'autore

Repository Staff Only: item control page