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NF-kappaB factor c-Rel mediates neuroprotection elicited by mGlu5 receptor agonists against amyloid beta-peptide toxicity.
NF-kappaB factor c-Rel mediates neuroprotection elicited by mGlu5 receptor agonists against amyloid beta-peptide toxicity.
- Source :
-
Cell death and differentiation [Cell Death Differ] 2005 Jul; Vol. 12 (7), pp. 761-72. - Publication Year :
- 2005
-
Abstract
- 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.
- Subjects :
- Animals
Cell Line, Tumor
Cell Survival drug effects
Cells, Cultured
Cerebral Cortex cytology
Enzyme Inhibitors pharmacology
Excitatory Amino Acid Agonists pharmacology
Gene Deletion
Gene Silencing
Glycine analogs & derivatives
Glycine pharmacology
Humans
Mice
Mice, Inbred C57BL
Neurons cytology
Neurons metabolism
Neurons pathology
Neuroprotective Agents metabolism
Phenylacetates pharmacology
Proto-Oncogene Proteins c-rel deficiency
Proto-Oncogene Proteins c-rel genetics
RNA, Small Interfering genetics
RNA, Small Interfering metabolism
Receptors, Metabotropic Glutamate genetics
Superoxide Dismutase metabolism
Amyloid beta-Peptides toxicity
NF-kappa B metabolism
Neurons drug effects
Neuroprotective Agents pharmacology
Proto-Oncogene Proteins c-rel metabolism
Receptors, Metabotropic Glutamate agonists
Receptors, Metabotropic Glutamate metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1350-9047
- Volume :
- 12
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Cell death and differentiation
- Publication Type :
- Academic Journal
- Accession number :
- 15818410
- Full Text :
- https://doi.org/10.1038/sj.cdd.4401598