2004 Fiscal Year Final Research Report Summary
Development of a drug, which can pass the blood-brain barrier and induces neuroprotective proteins in the brain.
| Project/Area Number |
15590925
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | NATIONAL CENTER FOR GERIATRICS AND GERONTOLOGY |
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Principal Investigator |
MARUYAMA Wakako National Center for Geriatrics and Gerontology, Department of Geriatric Medicine, Head, 老年病研究部, 部長 (20333396)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Neuroprotective drug / Neurotrophic factor / Parkinson's disease / Alzheimer's disease / Propargylamine / Transcription factor / Cerebrospinal fluid / Japanese monkey |
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| Research Abstract |
Propargylamine derivatives such as (-)deprenyl [selegiline] and rasagiline are developed as the selective inhibitors of type B monoamine oxidase (MAO-B). Among them, setegilie has been used clinicaly for the treatment of Parkinson's disease for MAO-B inhbitors expecting to increase neurotransmitter dopamine. The neuroprotective effects of protargylamines which is independent to enzyme inhibition have been reported by in vtro and in vivo experiments, but the molecular mechanism has not been elucidated. Using clonal neuroblastoma SH-SY5Y cells, apoptosis model was estabished and it was found that propargylamines protected the cells from mitchondria-dependent cell death by activating stress-responsible transcription factors such as NFkappaB. NFkappaB induced neuroprotective proteins such as neurotrophic fectors, BDNF and GDNF, BCL-2 and SOD. The neuroprotective effect of propargylamines may be ascribed to the induction of new proteins and the clinical effects of these drugs should be re-examined in concern wih this aspect. Neurotrophic factors are known to be secreted from the cells and their level in the cerebrospinal fluid(CSF) may correlate wih that in the brain. We admhistrated rasagiline [N-propargyl-1(R)-aminoindane] or saline to 4 Japanese monkeys respectively, and CSF was obtained once a week up to 8 weeks. Sight and transient increase of BDNF was observed but the difference was not marked. The further study to estimate optimum dose and period of the drugs to increase neuroprotective proteins is needed.
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Research Products
(25 results)
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[Journal Article] Neuroprotective function of R-(-)-(benzyofuran-2-yl) -2-propylamino-pentane, [R-(-)-BPAP], against apoptosis induced by N-methyl(R)salsolinol, an endogenous dopaminergic neurotoxin, in human dopaminergic neuroblastoma SH-SY5Y cells.2004
Author(s)
Maruyama W, Yi H, Takahashi T, Shimazu S, Ohde H, Yoneda K, Iwasa K, Naoi M.
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Journal Title
Life Sci. 21
Pages: 107-117
Description
「研究成果報告書概要(和文)」より
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[Journal Article] N-Propargyl-1(R)-aminoindan, rasagiline, increases glial cell line- derived neurotrophic factor (GDNF) in neuroblastoma SH-SY5Y cells through activation of NF-kappaB transcription factor.2004
Author(s)
Maruyama W, Nitta A, Shamoto-Nagai M, Hirata Y, Akao Y, Youdim M, Furukawa S, Nabeshima T, Naoi M.
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Journal Title
Neurochem.Int. 25
Pages: 193-204
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Neuroprotective function of R-(-)-(benzyofuran-2-yl)-2-propylatnino-pentane, R-(-)-BPAP], against apoptosis induced by N-methyl (R)salsolinol, an endogenous dopaminergic neurotoxin, in human dopaminergic neuroblastoraa SH-SY5Y cells.2004
Author(s)
W.Maruyama, H.Yi, T.Takahashi, S.Shimazu, H.Ohde, K.Yoneda, K.Iwasa, M.Naoi
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Journal Title
Life Sci. 21
Pages: 107-117
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Mitochondrial Genome Variation in Eastern Asia and the Peopling of Japan.
Author(s)
Tanaka M, V.M.Cabrera, A.M.Gonzalez, J.M.Larruga, Takeyasu T, Fuku N, L-J.Guo, Hirose R, Fujita Y, Kurata M, Shinoda K, Umetsu K, Yamada Y, Oshida Y, Sato Y, Hattori N, Mizuno Y, Arai Y, Hirose N, Ohta S, Ogawa O, Tanaka Y, Kawamori R, Shamoto-Nagai M, Maruyama W, Shimokata H, Suzuki R, Shimodaira H.
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Journal Title
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Mitochondrial Genome Variation in Eastern Asia and the Peopling of Japan.
Author(s)
M.Tanaka, V.M.Cabrera, A.M.Gonzalez, J.M.Larruga, T.Takeyasu, N.Fuku, L-J.Guo, R.Hirose, Y.Fujita, M.Kurata, K.Shinoda, K.Umetsu, Y.Yamada, Y.Oshida, Y.Sato, N.Hattori, Y.Mizuno, Y.Arai, N.Hirose, S.Ohta, O.Ogawa, Y.Tanaka, R.Kawamori, M.Shamoto-Nagai, W.Maruyama, H.Shimokata, R.Suzuki, H.Shimodaira
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Book] 神経保護薬2004
Author(s)
丸山和佳子, 直井信
Total Pages
165
Description
「研究成果報告書概要(和文)」より
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