title: Iduna protects the brain from glutamate excitotoxicity and stroke by interfering with poly(ADP-ribose) polymer-induced cell death.
abstract: 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.
authors: Neuroregeneration Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors: Shaida A
authors: SA
authors: Andrabi
authors: Ho Chul
authors: HC
authors: Kang
authors: Jean-François
authors: JF
authors: Haince
authors: Yun-Il
authors: YI
authors: Lee
authors: Jian
authors: J
authors: Zhang
authors: Zhikai
authors: Z
authors: Chi
authors: Andrew B
authors: AB
authors: West
authors: Raymond C
authors: RC
authors: Koehler
authors: Guy G
authors: GG
authors: Poirier
authors: Ted M
authors: TM
authors: Dawson
authors: Valina L
authors: VL
authors: Dawson
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