NF-kappa B factor c-Rel mediates neuroprotection elicited by mGlu5 receptor agonists against amyloid beta-peptide toxicity
2005 | journal article; research paper. A publication with affiliation to the University of Göttingen.
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NF-kappa B factor c-Rel mediates neuroprotection elicited by mGlu5 receptor agonists against amyloid beta-peptide toxicity
Pizzi, M.; Sarnico, I.; Boroni, F.; Benarese, M.; Steimberg, N.; Mazzoleni, G. & Dietz, G. P. H. et al. (2005)
Cell Death and Differentiation, 12(7) art. 1362. DOI: https://doi.org/10.1038/sj.cdd.4401598 10.1038/sj.cdd.4401742
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- Authors
- Pizzi, M.; Sarnico, I.; Boroni, F.; Benarese, M.; Steimberg, N.; Mazzoleni, G.; Dietz, G. P. H. ; Bähr, M. ; Liou, H. C.; Spano, P. F.
- Abstract
- Opposite effects of nuclear factor-kappa B (NF-kappa B) on neuron survival rely on activation of diverse NF-kappa B factors. While p65 is necessary for glutamate-induced cell death, c-Rel mediates prosurvival effects of interleukin-1 beta. However, it is unknown whether activation of c-Rel-dependent pathways reduces neuron vulnerability to amyloid-beta (A beta), a peptide implicated in Alzheimer's disease pathogenesis. We show that neuroprotection elicited by activation of metabotropic glutamate receptors type 5 (mGlu5) against A beta toxicity depends on c-Rel activation. A beta peptide induced NF-kappa B factors p50 and p65. The mGlu5 agonists activated c-Rel, besides p50 and p65, and the expression of manganese superoxide dismutase ( MnSOD) and Bcl-X-L. Targeting c-Rel expression by RNA interference suppressed the induction of both antiapoptotic genes. Targeting c-Rel or Bcl-XL prevented the prosurvival effect of mGlu5 agonists. Conversely, c-Rel overexpression or TAT-Bcl-X-L addition rescued neurons from A beta toxicity. These data demonstrate that mGlu5 receptor activation promotes a c-Rel-dependent antiapoptotic pathway responsible for neuroprotection against A beta peptide.
- Issue Date
- 2005
- Journal
- Cell Death and Differentiation
- ISSN
- 1350-9047
- Language
- English
- Notes
- Artikel (doi:10.1038/sj.cdd.4401598) mit Corrigendum (doi:10.1038/sj.cdd.4401742)