Gamma secretase-mediated Notch signaling worsens brain damage and functional outcome in ischemic stroke.
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.
Arumugam
Thiruma V
TV
Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, 5600 Nathan Shock Drive, Baltimore, Maryland 21224, USA.
Chan
Sic L
SL
Jo
Dong-Gyu
DG
Yilmaz
Gokhan
G
Tang
Sung-Chun
SC
Cheng
Aiwu
A
Gleichmann
Marc
M
Okun
Eitan
E
Dixit
Vishwa D
VD
Chigurupati
Srinivasulu
S
Mughal
Mohamed R
MR
Ouyang
Xin
X
Miele
Lucio
L
Magnus
Tim
T
Poosala
Suresh
S
Granger
D Neil
DN
Mattson
Mark P
MP