NF-κB factor c-Rel mediates neuroprotection elicited by mGlu5 receptor agonists againts amyloid β-peptide toxicity

M. Pizzi, I. Sarnico, F. Boroni, M. Benarese, N. Steimberg, G. Mazzoleni, G. P H Dietz, M. Bähr, H. C. Liou, P. F. Spano

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Pages (from-to)761-772
Number of pages12
JournalCell Death and Differentiation
Volume12
Issue number7
DOIs
Publication statusPublished - Jul 2005

Keywords

  • Amyloid-β
  • Bcl-X
  • CHPG
  • mGlu5 receptor
  • MnSOD
  • NF-κB

ASJC Scopus subject areas

  • Cell Biology

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