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
- 来源:
- 关键词:
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:
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 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:
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