2006 Fiscal Year Final Research Report Summary
Development of a novel therapy for brain infarction using a cell-penetrating protein exhibiting enhanced anti-cell death activity
| Project/Area Number |
16390257
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Nippon Medical School |
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Principal Investigator |
OHTA Shigeo Nippon Medical School, Graduate School of Medicine, Professor (00125832)
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| Co-Investigator(Kenkyū-buntansha) |
KATSURA Ken-ichiro Nippon Medical School, Dept. Internal Medicine, Senior Assistant Professor (50297892)
ASOH Sadamitsu Nippon Medical School, Institute of Gerontology, Assistant Professor (70167914)
KAMINURA Naoomi Nippon Medical School, Institute of Gerontology, Assistant Professor (60283800)
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| Project Period (FY) |
2004 – 2006
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| Keywords | mitochondria / PTD-FNK / brain infarction / ischemia / Protein therapy |
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| Research Abstract |
Many practical therapies have been explored for clinical applications to ischemic cerebral infarction; however, the most are still insufficient for treatments for acute stroke. We show here a potential combination therapy in a rat focal ischemic model to improve neurological symptoms as well as reduce infarct volumes at the maximum level. We applied a protein transduction technology using the artificial anti-death FNK protein fused with a protein-transduction-domain peptide (PTD-FNK). When PTD-FNK was administrated at1hr after initiating ischemia followed by the administration of an immunosuppressant FK506 with a 30-min time lag, infarct volumes of the total brain and cortex were markedly reduced to a level of 27% and 14%, respectively. This procedure not only reduced the infarct volume and edema, but also markedly improved neurological symptoms. The therapeutic effect continued at least for 1 week after ischemia. FK506 inhibited the transduction of PTD-FNK in vitro, which explains the requirement of a time lag for the administration of FK506. An additional in vitro experiment showed that PTD-FNK, when administered 30 min before FK506, gave the maximal protective effect through reducing an intracellular calcium concentration. We propose that this combination therapy would give a synergistic protective effect of both drugs, reducing adverse effect of FK506.
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