| Project/Area Number |
17300120
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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 | Gifu Pharmaceutical University |
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Principal Investigator |
NOMOTO Hiroshi Gifu Pharmaceutical University, Pharmaceutical Science, Associate professor, 薬学部, 助教授 (80164747)
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| Co-Investigator(Kenkyū-buntansha) |
FUKUMITSU Hidefumi Gifu Pharmaceutical University, Pharmaceutical Science, Assistant professor, 薬学部, 助手 (00308280)
FURUKAWA Shoei Gifu Pharmaceutical University, Pharmaceutical Science, Professor, 薬学部, 教授 (90159129)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥7,500,000 (Direct Cost: ¥7,500,000)
Fiscal Year 2006: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2005: ¥3,500,000 (Direct Cost: ¥3,500,000)
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| Keywords | neurotrophin / protein processing / nerve growth factor(NGF) / brain-derived neurotrophic factor(BDNF) / protein secretion / propeptide / oligosaccharides of glycoproteins / cell biology / プロセシング / NGF / BDNF / 分泌 / 糖鎖 / オートクライン / GDNF |
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| Research Abstract |
Neurotrophins, including NGF and BDNF, are secreted not only as mature forms but also as precursors. The two forms of neurotrophins exhibit opposite effects on neurons, namely survival or death. Therefore, the processing step from precursor to mature neurotrophin is extremely important. Following points have been examined.
1, Intramolecular sequence of neurotrophins that determined the processing efficiency was clarified. The C-terminal side of their pro-region was especially effective on their processing.
2, Intracellular proteins that affect the neurotrophin processing are now being screened on the basis of the interaction with proNGF.
3, The high density of cells stimulated partially the production of mature NGF, although the extracellular change of precursor to mature neurotrophin was negligible with the cultured cells. The expression of processing enzymes by high density cells is now being examined.
4, In order to construct sensitive EIA assay system of proNGF, uncleavable proNGF was produced by DNA recombinant technique in the insect cells, and its antibody is now being made. Such a sensitive EIA assay system should be useful since the production of pro-neurotrophins is considered to be linked to neurodegenerative diseases.
5, Oligosaccharides in the pro-region of NGF was found to be essential for the processing and secretion of NGF. The effect of the oligosaccharide location in propeptides on the processing and the metabolism of the aglyco-form of proNGF in cells is now being examined.
6, When NGF and its receptors were co-expressed in cells, the cells had a tendency to die. This suggests the intracellular interaction of NGF and its receptors occurred, which mechanism is now being examined.
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