Gamma secretase-mediated Notch signaling worsens brain damage and functional outcome in ischemic stroke
Journal
Nature Medicine
Journal Volume
12
Journal Issue
6
Pages
621-623
Date Issued
2006
Author(s)
Arumugam T.V.
Chan S.L.
Jo D.-G.
Yilmaz G.
Cheng A.
Gleichmann M.
Okun E.
Dixit V.D.
Chigurupati S.
Mughal M.R.
Ouyang X.
Miele L.
Magnus T.
Poosala S.
Granger D.N.
Mattson M.P.
Abstract
Mice transgenic for antisense Notch and normal mice treated with inhibitors of the Notch-activating enzyme γ-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. ? 2006 Nature Publishing Group.
SDGs
Other Subjects
2 [2 (3,5 difluorophenyl)acetylamino] n (5 methyl 6 oxodihydro 5h dibenzo[b,d]azepin 7 yl)propionamide; enzyme inhibitor; gamma secretase; Notch1 receptor; unclassified drug; animal cell; animal experiment; animal model; animal tissue; apoptosis; article; brain artery; brain cell; brain cortex; brain damage; brain function; cell activation; cell death; cell hypoxia; cell infiltration; cell stimulation; cell survival; cerebrovascular accident; controlled study; degenerative disease; drug efficacy; drug infusion; drug targeting; functional assessment; in vivo study; inflammation; intracellular space; ischemia; leukocyte; microglia; modulation; mouse; nerve cell; nerve cell plasticity; nervous system development; neurologic disease; neuroprotection; nonhuman; nucleic acid probe; outcome assessment; priority journal; reperfusion; signal transduction; transgenic mouse; wild type; Amyloid Precursor Protein Secretases; Animals; Apoptosis; Aspartic Endopeptidases; Brain; Brain Ischemia; Cells, Cultured; Cerebrovascular Accident; Endopeptidases; Enzyme Inhibitors; Humans; Leukocytes; Mice; Mice, Knockout; Mice, Transgenic; Microglia; Neurons; Peptides; Rats; Receptor, Notch1; Reperfusion Injury; Signal Transduction; Treatment Outcome
Type
journal article