NF-kappaB factor c-Rel mediates neuroprotection elicited by mGlu5 receptor agonists against amyloid beta-peptide toxicity
| Autor: | G. Mazzoleni, Marina Pizzi, Marina Benarese, G. P. H. Dietz, Mathias Bähr, F. Boroni, Ilenia Sarnico, Hsiou-Chi Liou, P. F. Spano, N. Steimberg |
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| Rok vydání: | 2005 |
| Předmět: |
Programmed cell death
Cell Survival Glycine Bcl-xL Biology Receptors Metabotropic Glutamate Neuroprotection chemistry.chemical_compound Mice Cell Line Tumor Excitatory Amino Acid Agonists Gene silencing Animals Humans Gene Silencing Enzyme Inhibitors RNA Small Interfering Receptor Molecular Biology Cells Cultured Phenylacetates Cerebral Cortex Neurons Amyloid beta-Peptides Superoxide Dismutase NF-kappa B NF-κB Cell Biology NFKB1 Molecular biology Proto-Oncogene Proteins c-rel Cell biology Mice Inbred C57BL Neuroprotective Agents chemistry Metabotropic glutamate receptor biology.protein Gene Deletion |
| Zdroj: | Università degli Studi di Brescia-IRIS |
| ISSN: | 1350-9047 |
| Popis: | Opposite effects of nuclear factor-kappaB (NF-kappaB) on neuron survival rely on activation of diverse NF-kappaB factors. While p65 is necessary for glutamate-induced cell death, c-Rel mediates prosurvival effects of interleukin-1beta. However, it is unknown whether activation of c-Rel-dependent pathways reduces neuron vulnerability to amyloid-beta (Abeta), a peptide implicated in Alzheimer's disease pathogenesis. We show that neuroprotection elicited by activation of metabotropic glutamate receptors type 5 (mGlu5) against Abeta toxicity depends on c-Rel activation. Abeta peptide induced NF-kappaB 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-X(L) prevented the prosurvival effect of mGlu5 agonists. Conversely, c-Rel overexpression or TAT-Bcl-X(L) addition rescued neurons from Abeta toxicity. These data demonstrate that mGlu5 receptor activation promotes a c-Rel-dependent antiapoptotic pathway responsible for neuroprotection against Abeta peptide. |
| Databáze: | OpenAIRE |
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