| Project/Area Number |
03454237
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Neurology
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| Research Institution | University of Tsukuba |
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Principal Investigator |
MIZUSAWA Hidehiro Tsukuba Univ., Neurology, Assoc.Prof., 臨床医学系, 助教授 (30144091)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIZAWA Toshihiro Tsukuba Univ., Neurology, Assist.Prof., 臨床医学系, 講師 (50212311)
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| Project Period (FY) |
1991 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥6,200,000 (Direct Cost: ¥6,200,000)
Fiscal Year 1993: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1992: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1991: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | Multiple system atrophy / argyrophilic inclusion / oligodendroglia / ubiquitin / alphaB-cystallin / ferric iron / Cu / Zu SOD / oxidative stress / αBクリスタル / 3価鉄 / ZnSOD |
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| Research Abstract |
Clinicopathological study of 6 brains of multiple system atrophy (MSA) revealed the precise distribution of glial cytoplasmic inclusions (GCIs) and a characteristic, laminar astrogliosis in the primary motor cortex, where a decrease in number of small to medium-sized neurons was found for the first time by a morphometric analysis.
GCIs were clearly immunostained for not only ubiquitin but also ubiquitin C-terminal hydrolase and 20S-/ 26S-proteasomes. The finding indictes that the main process of formation and degradation of GCIs is via ATP-dependent, non-lysosomal pathway.
Since oligodendroglia are involved in iron metabolism and iron is related to free radical formation, we investigated iron, ferritin and superoxide dismutase (SOD). In the MSA motor cortex, ferric iron was detected in microglia and macrophages with immunocytochemical localization of ferritin and Cu/Zu SOD within GCIs. These facts suggest first that GCIs might be related to neural death via oxidative stress.
In biochemical analysis, GCIs were partially purified from the MAS brain by sieving with mesh and discontinuous sucrose density gradient centrifugation. GCIs were mainly collected in the 45% to 50% sucrose interface which contained 32KDa and 40KDa proteins. These proteins were recognized with both anti-ubiquitin and anti-alpha B-cystallin antibodies, and not found in the identical fraction from the control brain. This is the first biochemical demonstration of alpha B-cystallin which might be ubiquitinated, as a component of GCI.
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