Iduna protects the brain from glutamate excitotoxicity and stroke by interfering with poly(ADP-ribose) polymer-induced cell death.

Journal Article (Journal Article)

Glutamate acting on N-methyl-D-aspartate (NMDA) receptors induces neuronal injury following stroke, through activation of poly(ADP-ribose) polymerase-1 (PARP-1) and generation of the death molecule poly(ADP-ribose) (PAR) polymer. Here we identify Iduna, a previously undescribed NMDA receptor-induced survival protein that is neuroprotective against glutamate NMDA receptor-mediated excitotoxicity both in vitro and in vivo and against stroke through interfering with PAR polymer-induced cell death (parthanatos). Iduna's protective effects are independent and downstream of PARP-1 activity. Iduna is a PAR polymer-binding protein, and mutation at the PAR polymer binding site abolishes the PAR binding activity of Iduna and attenuates its protective actions. Iduna is protective in vivo against NMDA-induced excitotoxicity and middle cerebral artery occlusion-induced stroke in mice. To our knowledge, these results define Iduna as the first known endogenous inhibitor of parthanatos. Interfering with PAR polymer signaling could be a new therapeutic strategy for the treatment of neurologic disorders.

Full Text

Duke Authors

Cited Authors

  • Andrabi, SA; Kang, HC; Haince, J-F; Lee, Y-I; Zhang, J; Chi, Z; West, AB; Koehler, RC; Poirier, GG; Dawson, TM; Dawson, VL

Published Date

  • June 2011

Published In

Volume / Issue

  • 17 / 6

Start / End Page

  • 692 - 699

PubMed ID

  • 21602803

Pubmed Central ID

  • PMC3709257

Electronic International Standard Serial Number (EISSN)

  • 1546-170X

Digital Object Identifier (DOI)

  • 10.1038/nm.2387


  • eng

Conference Location

  • United States