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Gamma secretase-mediated Notch signaling worsens brain damage and functional outcome in ischemic stroke.

Authors
  • Arumugam, Thiruma V
  • Chan, Sic L
  • Jo, Dong-Gyu
  • Yilmaz, Gokhan
  • Tang, Sung-Chun
  • Cheng, Aiwu
  • Gleichmann, Marc
  • Okun, Eitan
  • Dixit, Vishwa D
  • Chigurupati, Srinivasulu
  • Mughal, Mohamed R
  • Ouyang, Xin
  • Miele, Lucio
  • Magnus, Tim
  • Poosala, Suresh
  • Granger, D Neil
  • Mattson, Mark P
Type
Published Article
Journal
Nature medicine
Publication Date
Jun 01, 2006
Volume
12
Issue
6
Pages
621–623
Identifiers
PMID: 16680150
Source
Medline
License
Unknown

Abstract

Mice transgenic for antisense Notch and normal mice treated with inhibitors of the Notch-activating enzyme gamma-secretase showed reduced damage to brain cells and improved functional outcome in a model of focal ischemic stroke. Notch endangers neurons by modulating pathways that increase their vulnerability to apoptosis, and by activating microglial cells and stimulating the infiltration of proinflammatory leukocytes. These findings suggest that Notch signaling may be a therapeutic target for treatment of stroke and related neurodegenerative conditions.

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