Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Global cerebral ischemia/hypoxia, as can occur during human stroke, damages brain neural networks and synaptic functions. The recently demonstrated protein kinase C (PKC) activation-induced synaptogenesis in rat hippocampus suggested the potential of PKC-mediated antiapoptosis and synaptogenesis during conditions of neurodegeneration. Consequently, we examined the effects of chronic bryostatin-1, a PKC activator, on the cerebral ischemia/hypoxia-induced impairment of synapses and neurotrophic activity in the hippocampal CA1 area and on hippocampus-dependent spatial learning and memory. Postischemic/hypoxic bryostatin-1 treatment effectively rescued ischemia-induced deficits in synaptogenesis, neurotrophic activity, and spatial learning and memory. These results highlight a neuroprotective signaling pathway, as well as a therapeutic strategy with an extended time window for reducing brain damage due to stroke by activating particular PKC isozymes.
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PMID:Poststroke neuronal rescue and synaptogenesis mediated in vivo by protein kinase C in adult brains. 1876 86

Therapeutics for cerebral ischemia/hypoxia, which often results in ischemic stroke in humans, are a global unmet medical need. Here, we report that bryostatin-1, a highly potent protein kinase C (PKC) activator, interrupts pathophysiological molecular cascades and apoptosis triggered by cerebral ischemia/hypoxia, enhances neurotrophic activity, and induces synaptogenesis in rats. This postischemic therapeutic approach is further shown to preserve learning and memory capacity even 4 months later as well as long-term memory induced before the ischemic event. Our results of electromicroscopic and immunohistochemical analyses of neuronal and synaptic ultra-structure are consistent with a PKC-mediated synaptic remodeling and repair process that confers long-lasting preservation of spatial learning and memory before and after the cerebral ischemic/hypoxic event, suggesting a previously undescribed therapeutic modality for cerebral ischemia/hypoxia and ischemic stroke.
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PMID:Postischemic PKC activation rescues retrograde and anterograde long-term memory. 1966 90