2014 Fiscal Year Final Research Report
Study of neurotoxicity of activated human glial cells
| Project/Area Number |
24591721
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Psychiatric science
|
|---|
| Research Institution | Shimane University |
|---|
Principal Investigator |
|
|---|
| Research Collaborator |
MCGEER Patrick L. University of British Columbia, Department of Psychiatry, Professor Emeritus
|
|---|
| Project Period (FY) |
2012-04-01 – 2015-03-31
|
| Keywords | ヒトグリア細胞 / 炎症性活性化 / 神経毒性 / ヒストン脱アセチル化酵素阻害剤 / L型カルシウム拮抗剤 |
|---|
| 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.
|
| Free Research Field |
精神神経免疫
|
