Abstract
Opposite effects of nuclear factor-κB (NF-KB) on neuron survival rely on activation of diverse NF-κB factors. While p65 is necessary for glutamate-induced cell death, c-Rel mediates prosurvival effects of interleukin-1β. However, it is unknown whether activation of c-Rel-dependent pathways reduces neuron vulnerability to amyloid-β (Aβ), a peptide implicated in Alzheimer's disease pathogenesis. We show that neuroprotection elicited by activation of metabotropic glutamate receptors type 5 (mGlu5) against Aβ toxicity depends on c-Rel activation. Aβ peptide induced NF-κB factors p50 and p65. The mGlu5 agonists activated c-Rel, besides p50 and p65, and the expression of manganese superoxide dismutase (MnSOD) and Bcl-XL. 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-XL addition rescued neurons from Aβ toxicity. These data demonstrate that mGlu5 receptor activation promotes a c-Rel-dependent antiapoptotic pathway responsible for neuroprotection against Aβ peptide.
Original language | English |
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Pages (from-to) | 761-772 |
Number of pages | 12 |
Journal | Cell Death and Differentiation |
Volume | 12 |
Issue number | 7 |
DOIs | |
Publication status | Published - Jul 2005 |
Keywords
- Amyloid-β
- Bcl-X
- CHPG
- mGlu5 receptor
- MnSOD
- NF-κB
ASJC Scopus subject areas
- Cell Biology