| Project/Area Number |
16300121
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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 |
Neurochemistry/Neuropharmacology
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| Research Institution | Nagoya University |
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Principal Investigator |
SAWADA Makoto Nagoya University, Research Institute of Environmental Medicine, Professor (10187297)
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| Co-Investigator(Kenkyū-buntansha) |
ONO Kenji Nagoya University, Research Institute of Environmental Medicine, Assistant prof (80329698)
今井 文博 藤田保健衛生大学, 医学部, 講師 (20288476)
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| Project Period (FY) |
2004 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥13,660,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥960,000)
Fiscal Year 2007: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2006: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2005: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2004: ¥3,300,000 (Direct Cost: ¥3,300,000)
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| Keywords | microglia / brain-targeting molecule / chemical conjugates / brain-targeting tag |
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| Research Abstract |
It is known that a certain kind of cells can migrate into a specific target organ from blood flow when injected. They include brain-migrating cells such as neural stem cells, a part of bone marrow derived cells, lymphocytes and microglia. Microglia are subpopulation of glial cell in the brain and play important roles in the development, differentiation and maintenance of neural cells via their phagocytic activity and production of enzymes, cytokines and trophic factors. The mechanism of microglial brain migration is thought to be via a trans cellular pathway because microglial migration occur with out any breakage of the blood brain barrier. I found that microglia clone cells retain the capability to migrate into the brain from the circulation and that microglia can deliver the gene of interest to brain, by injecting microglia transfected galactosidase gene expressing vector to the circulation.
Meanwhile, I have successfully isolated several peptide which can mimic and/or compete the microglial brain-migrating activity. The peptides are small enough to be attached to several chemicals and biochemical materials and also to put in the sequence franking to recombinant protein as a brain-migrating tag. I indicated the ability of the peptides to penetrate through the BBB and distribute in brain parenchyma, therefore, the modified peptides are useful for the multi-purpose delivery tool to the brain, an availability of which was proved by several analyses including in vivo PET imaging.
Now I and my colleagues are trying to produce several brain-targeting drugs with our novel peptide. Our peptides may open the way of delivering into brain parenchyma even a compound as the PET-ligand with poor penetrability into brain. Further, we expect that our peptides offer the more flexibility in use for the delivery of many bio active materials into the brain.
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