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

Publication ,  Journal Article
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 in: Nat Med
June 2011

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.

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Published In

Nat Med

DOI

EISSN

1546-170X

Publication Date

June 2011

Volume

17

Issue

6

Start / End Page

692 / 699

Location

United States

Related Subject Headings

  • Stroke
  • Receptors, N-Methyl-D-Aspartate
  • Protein Binding
  • Poly(ADP-ribose) Polymerases
  • Poly Adenosine Diphosphate Ribose
  • Poly (ADP-Ribose) Polymerase-1
  • Nerve Tissue Proteins
  • Mitochondria
  • Mice
  • Immunology
 

Citation

APA
Chicago
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MLA
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Andrabi, S. A., Kang, H. C., Haince, J.-F., Lee, Y.-I., Zhang, J., Chi, Z., … Dawson, V. L. (2011). Iduna protects the brain from glutamate excitotoxicity and stroke by interfering with poly(ADP-ribose) polymer-induced cell death. Nat Med, 17(6), 692–699. https://doi.org/10.1038/nm.2387
Andrabi, Shaida A., Ho Chul Kang, Jean-François Haince, Yun-Il Lee, Jian Zhang, Zhikai Chi, Andrew B. West, et al. “Iduna protects the brain from glutamate excitotoxicity and stroke by interfering with poly(ADP-ribose) polymer-induced cell death.Nat Med 17, no. 6 (June 2011): 692–99. https://doi.org/10.1038/nm.2387.
Andrabi SA, Kang HC, Haince J-F, Lee Y-I, Zhang J, Chi Z, et al. Iduna protects the brain from glutamate excitotoxicity and stroke by interfering with poly(ADP-ribose) polymer-induced cell death. Nat Med. 2011 Jun;17(6):692–9.
Andrabi, Shaida A., et al. “Iduna protects the brain from glutamate excitotoxicity and stroke by interfering with poly(ADP-ribose) polymer-induced cell death.Nat Med, vol. 17, no. 6, June 2011, pp. 692–99. Pubmed, doi:10.1038/nm.2387.
Andrabi SA, Kang HC, Haince J-F, Lee Y-I, Zhang J, Chi Z, West AB, Koehler RC, Poirier GG, Dawson TM, Dawson VL. Iduna protects the brain from glutamate excitotoxicity and stroke by interfering with poly(ADP-ribose) polymer-induced cell death. Nat Med. 2011 Jun;17(6):692–699.

Published In

Nat Med

DOI

EISSN

1546-170X

Publication Date

June 2011

Volume

17

Issue

6

Start / End Page

692 / 699

Location

United States

Related Subject Headings

  • Stroke
  • Receptors, N-Methyl-D-Aspartate
  • Protein Binding
  • Poly(ADP-ribose) Polymerases
  • Poly Adenosine Diphosphate Ribose
  • Poly (ADP-Ribose) Polymerase-1
  • Nerve Tissue Proteins
  • Mitochondria
  • Mice
  • Immunology