Research for stress signalling underlying neuro-degenerating disease

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Acceleration of apoptosis and activation of caspases are observed in hippocalcin deficient hippocampal neurons. Here we examined the relation between hippocalcin and Hippocalcin and mixed lineage kinase (MLK)3, which is known to lead neuronal apoptosis.MLK3 were co-immunoprecipitated in a calcium-dependent manner. Immunocomplex kinase assay revealed that MLK3 kinase activity in hippocalcin deficient hippocampus was higher than that in wild type mice. In vitro kinase assay showed that recombinant hippocalcin inhibited MLK3 kinase activity in a calcium-dependent manner. Kainic acid-induced neuronal apoptosis was accelerated in hippocalcin deficient mice accompanied with enhancement in MLK3 activity. These results indicate that hippocalcin inhibits MLK3 kinase activity via direct interaction, and down-regulates apoptosis signaling in hippocampal neurons.