2024-03-29T14:22:19Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/365522021-06-07T10:56:54Zcom_10261_54com_10261_1col_10261_307
DIGITAL.CSIC
author
Fernández García, Ana María
author
Fernández, Silvia Venero
author
Carrero, P.
author
García-García, Miguel
author
Torres Alemán, Ignacio
2011-06-06T14:39:31Z
2011-06-06T14:39:31Z
2007
Journal of Neuroscience 27 (33): 8745-8756 (2007)
0270-6474
http://hdl.handle.net/10261/36552
10.1523/JNEUROSCI.1002-07.2007
1529-2401
Maladaptive inflammation is a major suspect in progressive neurodegeneration, but the underlying mechanisms are difficult to envisage in part because reactive glial cells at lesion sites secrete both proinflammatory and anti-inflammatory mediators. We now report that astrocytes modulate neuronal resilience to inflammatory insults through the phosphatase calcineurin. In quiescent astrocytes, inflammatory mediators such as tumor necrosis factor-alpha (TNF-alpha) recruits calcineurin to stimulate a canonical inflammatory pathway involving the transcription factors nuclear factor kappaB (NFkappaB) and nuclear factor of activated T-cells (NFAT). However, in reactive astrocytes, local anti-inflammatory mediators such as insulin-like growth factor I also recruit calcineurin but, in this case, to inhibit NFkappaB/NFAT. Proof of concept experiments in vitro showed that expression of constitutively active calcineurin in astrocytes abrogated the inflammatory response after TNF-alpha or endotoxins and markedly enhanced neuronal survival. Furthermore, regulated expression of constitutively active calcineurin in astrocytes markedly reduced inflammatory injury in transgenic mice, in a calcineurin-dependent manner. These results suggest that calcineurin forms part of a molecular pathway whereby reactive astrocytes determine the outcome of the neuroinflammatory process by directing it toward either its resolution or its progression
eng
openAccess
Calcineurin
neuroinflammation
Astrocytes
inflammatory cytokines
insulin-like growth factor I
neuronal death
Calcineurin in Reactive Astrocytes Plays a Key Role in the Interplay between Proinflammatory and Anti-Inflammatory Signals
artículo
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URL
https://digital.csic.es/bitstream/10261/36552/1/Fernandez%2cA.J.Neurosci%2c2007.pdf
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Fernandez,A.J.Neurosci,2007.pdf.txt