Targeting IKK2 by pharmacological inhibitor AS602868 prevents excitotoxic injury to neurons and oligodendrocytes

I. Sarnico, F. Boroni, M. Benarese, M. Alghisi, A. Valerio, L. Battistin, P. Spano, M. Pizzi

Research output: Contribution to journalArticle

Abstract

Among the diverse mechanisms involved in the pathophysiology of post-ischemic and post-traumatic injuries, excitotoxicity and nuclear factor-κB (NF-κB) activation through induction of IκB kinase (IKK) complex have a primary role. We investigated the effects of the selective inhibitor of the IKK2 subunit, the anilinopyrimidine derivative AS602868, on excitotoxic injury produced in rat organotypic hippocampal slices and cerebellar primary neurons. Brief exposure to N-methyl-d-aspartate (NMDA) induces astrocyte reactivity, neuron cell death and oligodendrocyte degeneration in hippocampal slices. Application of AS602868 elicited a long-lasting protection of both neurons and oligodendrocytes. Maximal effect was observed with prolonged application of the compound after NMDA exposure. Neuroprotection was also evident in primary cultures of cerebellar granule cells starting from 20 nM concentration. AS602868-elicited neuroprotection correlated with inhibition of NF-κB activity. Our results suggest that AS602868 may prove to be a valuable approach in treating neurodegeneration and demyelination associated with cerebral trauma and ischemia.

Original languageEnglish
Pages (from-to)693-701
Number of pages9
JournalJournal of Neural Transmission
Volume115
Issue number5
DOIs
Publication statusPublished - May 2008

Keywords

  • Anilinopyrimidine
  • AS602868
  • Glutamate
  • Hippocampal slices
  • IKK2
  • NF-κB

ASJC Scopus subject areas

  • Neuroscience(all)

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    Sarnico, I., Boroni, F., Benarese, M., Alghisi, M., Valerio, A., Battistin, L., Spano, P., & Pizzi, M. (2008). Targeting IKK2 by pharmacological inhibitor AS602868 prevents excitotoxic injury to neurons and oligodendrocytes. Journal of Neural Transmission, 115(5), 693-701. https://doi.org/10.1007/s00702-007-0016-1