| Project/Area Number |
09835008
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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 |
老化(加齢)
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| Research Institution | KOBE UNIVERSITY |
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Principal Investigator |
MATSUMOTO Akira KOBE UNIV., SCH.OF MED., ASSIT PROF., 医学部, 助教授 (80181759)
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| Project Period (FY) |
1997 – 1998
|
| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1997: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | ALZHEIMER'S DISEASE / beta-AMYLOID / SERINE PROTEASE / SECRETASE / NATURAL SUBSTRATE / SULFATED GLYCOCONJUGATE / 脳老化 |
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| Research Abstract |
Genetation of beta-amyloid (Abeta) from native precursor protein (APP) and its accumulation which appear as senile plaque and amyloid angiopathy in human brain are essentially associated with normal aging and pathophysiology of Alzheimer's disease. Processing of APP and formation of Abeta-bearing peptides were comparatively analyzed between normal lymphoblastoid cells and those derived from familial AD patients. 68 kDa serine protease was purified from culture medium of AD cells, which cleaves oligopeptides at the Abeta-N-terminus. Though this protease cleaves native LAPP in the vicinity of Abeta-N- terminus, native brain APP was not degraded, suggesting a strict tissue specificity in APP proteolysis. I searched for activities capable of cleaving native brain APP in human hippocampus, and HBP49 proteolytic activity was isolated and characterized, and the molecular cloning clarified as being a novel protease. Biochemical and molecular biological analyses suggested a physiological function of the protease in brain APP degradation and generation of Abeta peptides, and a possible role of sulfated glycocon-jugates attached to brain APP in the proteolysis. Immunohistochemical study showed its expression in neuronal perikarya, and some unique lesions with the immunoreactivity were found in brains of sporadic AD patients.
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