课题基金 / 基金详情

STRUCTURAL ASPECTS OF APP FUNCTION AND PATHOLOGY

STRUCTURAL ASPECTS OF APP FUNCTION AND PATHOLOGY
应用程序功能和病理学的结构方面
批准号:
2442269
负责人:
STEPHEN P ANDERSON
金额:
$23.0万
依托单位国家:
美国
项目类别:
财政年份:
1992
资助国家:
美国
项目状态:
已结题
起止时间:
1992-09-30 至 1999-06-30

项目摘要

项目成果

STEPHEN P ANDERSON的其他基金

相似基金

相关文献

中文摘要
翻译
描述(改编自申请人摘要)
英文摘要
DESCRIPTION (Adapted from the applicant's abstract) The long-term objective of this application is determination of the three dimensional structure of APP by analysis of the structures of its individual functional domains. The cysteine-rich N-terminal domain has been expressed at high levels and purified to homogeneity. Optimization of expression constructs will be required for production of material suitable for X-ray crystallography and NMR. In order to better understand the physiological behavior of APP -- both in normal tissue and in the context of Alzheimer's disease -- attempts are being made to identify APP binding proteins in the body. The concentration is on isolating potential proteases that interact with the APP Kunitz inhibitor (APP-KI) domain. Successful cloning of one such candidate protease utilizing a directed cloning approach has been accomplished. The present application proposes to continue this search until a comprehensive inventory of all human serine proteases capable of interacting with APP-KI has been completed. This will enable establishment of the role that these proteases play in human disease. Related work is concerned with investigating the interactions of the Alzheimer's amyloid beta peptide and its fibrils with fibrin(ogen)-binding proteins. This group of investigators recently discovered that the amyloid beta peptide is a potent stimulator of human tissue plasminogen activator. This property of the beta peptide may in part explain the association of deposits of beta peptide in the cerebral vasculature (cerebral amyloid angiopathy) with hemorrhagic strokes, especially those that occur in conjunction with thrombolytic therapy. These findings also provide a basis for understanding the hemorrhagic phenotype of the genetic disease, hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D). In the work proposed in this application, a plan for mapping the functional epitopes on the amyloid beta peptide that account for its fibrin(ogen) mimicry, and the development of monoclonal antibodies that block the interaction of beta peptide with fibrin(ogen)-binding molecules were described. In addition, the design of amyloid beta peptide analogues that form soluble "minifibrils" amenable to structural analysis by high resolution methods was described. Finally, these investigators intend to explore whether synergistic interactions occur in the CNS between fibrin(ogen)-binding proteins and beta amyloid that may have relevance to Alzheimer's disease.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
STRUCTURAL ASPECTS OF ABPP FUNCTION AND PATHOLOGY
  • 批准号:
    2052722
  • 项目类别:
  • 资助金额:
    $30.28万
  • 财政年份:
    1992
  • 负责人:
    STEPHEN P ANDERSON
  • 依托单位:
STRUCTURAL ASPECTS OF APP FUNCTION AND PATHOLOGY
  • 批准号:
    2732539
  • 项目类别:
  • 资助金额:
    $23.91万
  • 财政年份:
    1992
  • 负责人:
    STEPHEN P ANDERSON
  • 依托单位:
STRUCTURAL ASPECTS OF APP FUNCTION AND PATHOLOGY
  • 批准号:
    2052723
  • 项目类别:
  • 资助金额:
    $22.25万
  • 财政年份:
    1992
  • 负责人:
    STEPHEN P ANDERSON
  • 依托单位:
STRUCTURAL ASPECTS OF ABPP FUNCTION AND PATHOLOGY
  • 批准号:
    3123436
  • 项目类别:
  • 资助金额:
    $28.92万
  • 财政年份:
    1992
  • 负责人:
    STEPHEN P ANDERSON
  • 依托单位:
海外基金