Caveolin-1/lGF-IR Interactions in Oligodendrocytes

少突胶质细胞中的 Caveolin-1/lGF-IR 相互作用

基本信息

  • 批准号:
    6368300
  • 负责人:
  • 金额:
    $ 16.97万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2002
  • 资助国家:
    美国
  • 起止时间:
    2002-01-15 至 2006-12-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Multiple Sclerosis (MS) is characterized by patchy demyelination within the central nervous system. Remyelination is often incomplete, and the failure of OLGs to remyelinate is at least in part due to OLG programmed cell death (PCD). Caveolin-1 is likely to modulate OLG function and survival. Caveolin-1 forms the structural backbone of caveolae vesicles and has diverse effects on signal transduction, cholesterol transport, cell cycle control, and PCD. By binding to signaling proteins via a region termed the caveolinscaffolding domain (CSD), caveolin-1 regulates (generally inhibits) signal transduction. The CSD binds to conserved regions of signaling molecules, such as the caveolin-binding domain (CBD) of receptor tyrosine kinases. We have previously shown that caveolin-1 expression by Schwann cells increases during development and decreases following nerve transection, which is consistent with findings by others that caveolin-1 expression is differentiation-dependent. Caveolin-1's expression and function in OLGs has not been studied. Insulinlike growth factor I (IGF-I) plays a vital role in OLG development, enhancing myelination and remyelination by OLGs, protecting OLGs from PCD, and preventing demyelination, but the underlying molecular mechanisms are poorly understood. We provide preliminary evidence that caveolin-1 binds to the IGF-I receptor (IGF-IR), contains a putative CBD, and is tyrosine phosphorylated following IGF-IR activation. We have 4 Specific Aims: 1) Analyze IGF-IR signaling and caveolin-1-IGF-IR interactions in OLGs, 2) investigate the effects of caveolin-1 expression and caveolin-1 tyrosine phosphorylation on IGF-IR-mediated signaling, proliferation, differentiation, and susceptibility to PCD, 3) characterize caveolin-1-IGF-IR interactions in OLGs, examining effects on IGFIRmediated signaling, proliferation, differentiation and PCD, and 4) investigate the consequences of caveolin-1-IGF-IR interactions in OLGs in vivo. At the end of these studies, we will better understand caveolin-1's regulation of IGF-IR signaling in OLGs and IGF-IR mediated proliferation, differentiation and neuroprotection of OLGs. Understanding the interplay between the IGF-IR and caveolin-1 and their control of OLG phenotype will provide insight into the molecular basis of myelination by OLGs and, hopefully, guide new treatments for MS.
描述(由申请人提供):多发性硬化症(MS)的特征

项目成果

期刊论文数量(0)
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DANIEL D MIKOL其他文献

DANIEL D MIKOL的其他文献

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{{ truncateString('DANIEL D MIKOL', 18)}}的其他基金

EFFECT OF BODY COOLING BY RTX ON MOTOR FUNCTION IN HEAT-SENSITIVE MS PATIENTS
RTX 身体冷却对热敏性多发性硬化症患者运动功能的影响
  • 批准号:
    7603791
  • 财政年份:
    2007
  • 资助金额:
    $ 16.97万
  • 项目类别:
Caveolin-1/lGF-IR Interactions in Oligodendrocytes
少突胶质细胞中的 Caveolin-1/lGF-IR 相互作用
  • 批准号:
    6620105
  • 财政年份:
    2002
  • 资助金额:
    $ 16.97万
  • 项目类别:
Caveolin-1/lGF-IR Interactions in Oligodendrocytes
少突胶质细胞中的 Caveolin-1/lGF-IR 相互作用
  • 批准号:
    6701805
  • 财政年份:
    2002
  • 资助金额:
    $ 16.97万
  • 项目类别:
OLIGODENDROCYTE/MYELIN GLYCOPROTEIN AND THE P
少突细胞/髓磷脂糖蛋白和 P
  • 批准号:
    2036479
  • 财政年份:
    1996
  • 资助金额:
    $ 16.97万
  • 项目类别:
OLIGODENDROCYTE/MYELIN GLYCOPROTEIN AND THE P
少突细胞/髓磷脂糖蛋白和 P
  • 批准号:
    2609531
  • 财政年份:
    1996
  • 资助金额:
    $ 16.97万
  • 项目类别:
OLIGODENDROCYTE/MYELIN GLYCOPROTEIN AND THE P
少突细胞/髓磷脂糖蛋白和 P
  • 批准号:
    6330371
  • 财政年份:
    1996
  • 资助金额:
    $ 16.97万
  • 项目类别:
OLIGODENDROCYTE/MYELIN GLYCOPROTEIN AND THE P
少突细胞/髓磷脂糖蛋白和 P
  • 批准号:
    6126058
  • 财政年份:
    1996
  • 资助金额:
    $ 16.97万
  • 项目类别:
OLIGODENDROCYTE/MYELIN GLYCOPROTEIN AND THE P
少突细胞/髓磷脂糖蛋白和 P
  • 批准号:
    2839249
  • 财政年份:
    1996
  • 资助金额:
    $ 16.97万
  • 项目类别:

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ROLE OF CELL ADHESION IN BIOLOGICAL SIGNAL TRANSDUCTION
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  • 批准号:
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  • 财政年份:
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  • 项目类别:
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  • 项目类别:
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