| Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Outline of Final Research Achievements |
Using primary culture of human glial a cells, we studied inflammatory activation processes of glial cells, which induce neurotoxicity, and identified the drugs that inhibited the glial neurotoxicity. The histone deacetylase inhibitor suberoylanilide hydroxamic acid significantly attenuated the neurotoxicity of astrocytes activated by IFN-γ. L-type calcium channel blockers significantly suppressed neurotoxic secretions from activated human astrocytes and microglia. These drugs reduced the STAT3 phosphorylation at the tyrosine-705 residue in the IFN-γ-activated astrocytes.
These findings suggest that neurotoxicity of human astrocytes is mediated by STAT3 phosphorylationboth and that both histone deacetylase inhibitors and L-type calcium channel blockers could be a useful treatment option for a broad spectrum of neurodegenerative diseases. Moreover, the tyrosine-705 residue in STAT3 could be a molecular target to develop new drugs for treatment of neurodegenerative disorders.
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