Iduna protects the brain from glutamate excitotoxicity and stroke by interfering with poly(ADP-ribose) polymer-induced cell death.
Published
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
- 21602803
Electronic International Standard Serial Number (EISSN)
- 1546-170X
Digital Object Identifier (DOI)
- 10.1038/nm.2387
Language
- eng
Conference Location
- United States