2002 Fiscal Year Final Research Report Summary
Analyses on beta-site APP cleaving enzyme (BACE1) of amyloid β protein deposited in brains of patients with Alzheimer's disease
| Project/Area Number |
12670590
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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 | University of Tsukuba |
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Principal Investigator |
TAMAOKA Akira University of Tsukuba, Deoartment of Neurology, Associate Professor (50192183)
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| Co-Investigator(Kenkyū-buntansha) |
MOCHIZUKI Akihide University of Tsukuba, 臨床医学系, Assistant Professor (40301080)
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| Project Period (FY) |
2000 – 2002
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| Keywords | Alzheimer's disease / amyloid β protein / BACE1 / APP |
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| Research Abstract |
Alzheimer's disease (AD) is characterized by the extensive deposition of amyloid β protein (Aβ) in brain cortex. Aβ is produced from β-amyloid precursor protein (APP) by β-secretase and γ-secretase. Recently, β-secretase was identified as beta-site APP cleaving enzyme 1 (BACE1). Inhibition against BACE1 activity could decrease Aβ generation, indicating the possibility that antagonistic drugs for BACE1 are therapeutic tools for AD.
We produced rabbit polyclonal antibodies against synthetic peptides of BACE1. Using these antibodies (aniti-BACE1 antibodies), BACE1 was characterized in human brains (temporal lobes) by Western blotting and immunohistochemistry.
All brain fractions extracted by Tris-saline, 1% Triton X-100 and 0.5% SDS sequentialy were revealed to contain BACE1. In order to compare amounts of BACE1 between AD and control brains, brain samples were directly extracted by 0.5% SDS and analyzed by Western blotting and densitometer. Although the mean level of amounts of BACE1 per m
… More
g protein in AD brains was significantly decreased, the ratio of BACE1 to MAP2 was significantly increased compared to control brains, indicating that remaining small numbers of neurons in AD brains might generate more amounts of BACE1 than control brain neurons. Digestion of both human brains and recombinant BACE1 by N-glycosidase F altered the molecular weight of BACE1 from 70 to 50kDa, consisting with calculated molecular weight of BACE1 depending on its amino acid residues, suggesting that human brains contained both unmodified BACE1 and its glycosylated form. Immunocytochemical studies employing anti-GFAP and anti-MAP2 antibodies as well as anti-BACE1 antibodies have shown that BACE1 was expressed exclusively in neurons.
Taking all these findings together in consideration, remaining neurons after neuronal loss in AD brains might generate more amounts of BACE1 than in controls, indicating that increased activities of BACE1 could be one of the causes of AD, which could justify the development of anti-BACE1 drugs for AD treatment. Less
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Research Products
(77 results)
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[Book] 新体系看護学2003
Author(s)
玉岡晃
Total Pages
12
Publisher
紫芝良昌・黒岩義之編,メヂカルフレンド社
Description
「研究成果報告書概要(和文)」より
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[Book] 難病の指針(第4版)2002
Author(s)
玉岡晃
Total Pages
7
Publisher
茨城県医師会難病の指針編集委員会(発行人佐藤怜)
Description
「研究成果報告書概要(和文)」より
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[Book] 神経内科学書
Author(s)
玉岡晃
Publisher
豊倉康夫編、朝倉書店(発表予定)
Description
「研究成果報告書概要(和文)」より
