Proceedings of the National Academy of Sciences · 2003 · 405 citations · 38 references
Life SciencesNeurobiologyNeuroscienceApoptosisCell SignalingMolecular NeuroscienceAcute Ischemic StrokeApoptotic SignalingHypoxic-ischemic Brain InjuryHypoxic-ischemic EncephalopathyNeuroprotectionStrokeC-jun N-terminal Kinase SignalingCerebral Hypoxic-ischemic InjuryCerebral Ischemia NeuroprotectionJnk Signaling PathwayJnk-mediated ApoptosisJun N-terminal Kinase SignalingStress-induced ApoptosisStroke Neuroprotection
c-Jun N-terminal kinase (JNK) signaling is an important contributor to stress-induced apoptosis, but it is unclear whether JNK and its isoforms (JNK1, JNK2, and JNK3) have distinct roles in cerebral ischemia. Here we show that JNK1 is the major isoform responsible for the high level of basal JNK activity in the brain. In contrast, targeted deletion of Jnk3 not only reduces the stress-induced JNK activity, but also protects mice from brain injury after cerebral ischemia-hypoxia. The downstream mechanism of JNK3-mediated apoptosis may include the induction of Bim and Fas and the mitochondrial release of cytochrome c. These results suggest that JNK3 is a potential target for neuroprotection therapies in stroke.
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The stress-activated protein kinase subfamily of c-Jun kinases
John Kyriakis, Papia T. Banerjee, Eleni Nikolakaki et al. · Nature · 1994 · 2.6K citations