NF-κB in innate neuroprotection and age-related neurodegenerative diseases

Annamaria Lanzillotta, Vanessa Porrini, Arianna Bellucci, Marina Benarese, Caterina Branca, Edoardo Parrella, Pier Franco Spano, Marina Pizzi

Research output: Contribution to journalArticlepeer-review

Abstract

NF-κB factors are cardinal transcriptional regulators of inflammation and apoptosis, involved in the brain programing of systemic aging and in brain damage. The composition of NF-κB active dimers and epigenetic mechanisms modulating histone acetylation, finely condition neuronal resilience to brain insults. In stroke models, the activation of NF-κB/c-Rel promotes neuroprotective effects by transcription of specific anti-apoptotic genes. Conversely, aberrant activation of NF-κB/RelA showing reduced level of total acetylation, but site-specific acetylation on lysine 310, triggers the expression of pro-apoptotic genes. Constitutive knockout of c-Rel shatters the resilience of substantia nigra (SN) dopaminergic (DA) neurons to aging and induces a parkinsonian like pathology in mice. c-rel-/- mice show increased level of aberrantly acetylated RelA in the basal ganglia, neuroinflammation, accumulation of alpha-synuclein, and iron. Moreover, they develop motor deficits responsive to l-DOPA treatment and associated with loss of DA neurons in the SN. Here, we discuss the effect of unbalanced activation of RelA and c-Rel during aging and propose novel challenges for the development of therapeutic strategies in neurodegenerative diseases.

Original languageEnglish
Article number00098
JournalFrontiers in Neurology
Volume6
Issue numberMAY
DOIs
Publication statusPublished - 2015

Keywords

  • BDNF
  • C-Rel deficient mice
  • Epigenetic drugs
  • NF-κB
  • RelA (K310)

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

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