MEGAKARYOCYTE/PLATELET AMYLOID BETA PROTEIN PRECURSOR

巨核细胞/血小板淀粉样β蛋白前体

基本信息

  • 批准号:
    2028837
  • 负责人:
  • 金额:
    $ 26.49万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    1992
  • 资助国家:
    美国
  • 起止时间:
    1992-09-30 至 1998-08-31
  • 项目状态:
    已结题

项目摘要

Alzheimer's disease (AD) is an idiopathic progressive dementia affecting a large proportion of our increasingly aged population. Although the pathogenesis of AD is not completely understood, present data suggest that it probably involves the abnormal proteolytic cleavage of a large precursor protein to yield about 42 residue protein, referred to as amyloid Beta protein or A4, which subsequently polymerizes and forms the amyloid deposits characteristic of this disease. The precursor of the amyloid Beta-protein (i.e., amyloid Beta-protein precursor; APP) is encoded by at least three mRNAs that arise through alternative splicing of two exons. The two most abundantly expressed forms contain a 56 residue insert, which has significant homology with the Kunitz-type protease inhibitors (KPI). Platelet coagulation Factor Xla-inhibitor was recently identified to be a form of APP that contains the KPI domain. Presently, little information exists on the origin of APP in the platelet or its processing during the maturation of megakaryocytes/platelets. The long-term objective of the work described in this application is to provide a detailed understanding of the production and processing of APP associated with megakaryocytes/platelets. Immunologic probes will be developed against specific regions of the APP molecule and utilized in immunofluorescent and immunoelectron microscopic techniques to define the cellular distribution of APP in (i) intact platelets, (ii) platelets during adhesion/aggregation reactions, (iii) megakaryocytic cell lines, and (iv) freshly isolated and cultured bone marrow megakaryocytes as they mature. The forms of APP present in intact platelets, as well as the processing of APP that occurs during platelet adhesion/aggregation reactions, will be analyzed utilizing immunoblotting protocols and radioimmunoassays. These studies will form the framework for analyzing the location and forms of APP associated with abnormal platelets that are present in the blood of AD patients. The origin of platelet APP will then be defined by utilizing immunologic assays and metabolic labeling/immunoprecipitation experiments to analyze the production of APP during the differentiation of megakaryocytic cell lines and bone marrow-derived cells in vitro. These studies will be complemented by characterizing the protease activity(ies) responsible for the processing of megakaryocyte/platelet APP. Furthermore, the structural domain(s) on APP that are critical for its targeting into platelet alpha-granules will be defined by the use of expression vector/APP constructs in cell lines that exhibit a storage secretory pathway. These constructs will include deletion mutants of APP, site-directed mutants of APP, and hybrid APP molecules. Because platelets have been proposed as a peripheral model for neurons, it is expected that information on the mechanisms by which megakaryocytes/platelets process APP will likely provide an insight into the expression and cleavage of this protein by neurons.
阿尔茨海默病(AD)是一种特发性进行性痴呆

项目成果

期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Expression of Kunitz protease inhibitor--containing forms of amyloid beta-protein precursor within vascular thrombi.
库尼茨蛋白酶抑制剂的表达——含有淀粉样β-蛋白前体形式在血管血栓内的表达。
  • DOI:
    10.1161/01.cir.94.11.2728
  • 发表时间:
    1996
  • 期刊:
  • 影响因子:
    37.8
  • 作者:
    Lang,IM;Moser,KM;Schleef,RR
  • 通讯作者:
    Schleef,RR
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RAYMOND R SCHLEEF其他文献

RAYMOND R SCHLEEF的其他文献

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{{ truncateString('RAYMOND R SCHLEEF', 18)}}的其他基金

MEGAKARYOCYTE/PLATELET AMYLOID BETA-PROTEIN PRECURSOR
巨核细胞/血小板淀粉样β-蛋白前体
  • 批准号:
    3368689
  • 财政年份:
    1992
  • 资助金额:
    $ 26.49万
  • 项目类别:
PLATELET PLASMINOGEN ACTIVATOR INHIBITORS
血小板纤溶酶原激活剂抑制剂
  • 批准号:
    3365042
  • 财政年份:
    1992
  • 资助金额:
    $ 26.49万
  • 项目类别:
MEGAKARYOCYTE/PLATELET AMYLOID BETA PROTEIN PRECURSOR
巨核细胞/血小板淀粉样β蛋白前体
  • 批准号:
    2225647
  • 财政年份:
    1992
  • 资助金额:
    $ 26.49万
  • 项目类别:
PLATELET PLASMINOGEN ACTIVATOR INHIBITORS
血小板纤溶酶原激活剂抑制剂
  • 批准号:
    3365043
  • 财政年份:
    1992
  • 资助金额:
    $ 26.49万
  • 项目类别:
PLATELET TYPE 1 PLASMINOGEN ACTIVATOR INHIBITOR
1 型血小板纤溶酶原激活剂抑制剂
  • 批准号:
    2028589
  • 财政年份:
    1992
  • 资助金额:
    $ 26.49万
  • 项目类别:
PLATELET TYPE 1 PLASMINOGEN ACTIVATOR INHIBITOR
1 型血小板纤溶酶原激活剂抑制剂
  • 批准号:
    6139154
  • 财政年份:
    1992
  • 资助金额:
    $ 26.49万
  • 项目类别:
MEGAKARYOCYTE/PLATELET AMYLOID BETA-PROTEIN PRECURSOR
巨核细胞/血小板淀粉样β-蛋白前体
  • 批准号:
    3368690
  • 财政年份:
    1992
  • 资助金额:
    $ 26.49万
  • 项目类别:
PLATELET TYPE 1 PLASMINOGEN ACTIVATOR INHIBITOR
1 型血小板纤溶酶原激活剂抑制剂
  • 批准号:
    2857804
  • 财政年份:
    1992
  • 资助金额:
    $ 26.49万
  • 项目类别:
MEGAKARYOCYTE/PLATELET AMYLOID BETA PROTEIN PRECURSOR
巨核细胞/血小板淀粉样β蛋白前体
  • 批准号:
    2225646
  • 财政年份:
    1992
  • 资助金额:
    $ 26.49万
  • 项目类别:
PLATELET PLASMINOGEN ACTIVATOR INHIBITORS
血小板纤溶酶原激活剂抑制剂
  • 批准号:
    2222574
  • 财政年份:
    1992
  • 资助金额:
    $ 26.49万
  • 项目类别:

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Solid State NMR Studies of Amyloid Proteins
淀粉样蛋白的固态核磁共振研究
  • 批准号:
    10446323
  • 财政年份:
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  • 资助金额:
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  • 项目类别:
Solid State NMR Studies of Amyloid Proteins
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  • 批准号:
    16H06216
  • 财政年份:
    2016
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阐明在金属存在下有毒的植物淀粉样蛋白的聚集和毒性机制
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    23380192
  • 财政年份:
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淀粉样蛋白异常构象转变的演示及其作为早期诊断工具的应用
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  • 财政年份:
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淀粉样蛋白的代谢和检测淀粉样蛋白的方法
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  • 财政年份:
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  • 批准号:
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  • 财政年份:
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