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SITE-SPECIFIC STUDIES PROVIDE STRUCTURAL INFORMATION ON AMYLOID BETA OLIGOMERS

SITE-SPECIFIC STUDIES PROVIDE STRUCTURAL INFORMATION ON AMYLOID BETA OLIGOMERS
特定位点研究提供了淀粉样β低聚物的结构信息
批准号:
8170990
负责人:
Charles G. Glabe
金额:
$1.8万
依托单位国家:
美国
项目类别:
财政年份:
2010
资助国家:
美国
项目状态:
已结题
起止时间:
2010-08-01 至 2011-07-31

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中文摘要
翻译
这个子项目是众多研究子项目之一
英文摘要
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Aggregation of Abeta peptides is a major contributor to Alzheimer's disease. Oligomeric forms of these peptides are especially interesting due to their high neurotoxicity and potentially important role in disease progression. However, very little structural information is currently available on Abeta oligomers. We have previously established that Abeta oligomers can be divided into at least two structural classes (prefibrillar and fibrillar oligomers) based on their reactivity with conformational antibodies. Here we compared both site-specific and global conformational stability of Abeta 40 fibrils and both classes of oligomers. To measure the site-specific stability, we introduced cysteine residues throughout the sequence of Abeta 40, labeled the new cysteines with the fluorescent dye acrylodan, and investigated their environment within the aggregates in guanidine thiocyanate-induced denaturation experiments. We found that Abeta 40 fibrils show high stability towards denaturation and moderate hydrophobicity in the 15-35 region with the exception of residues 25-30. This pattern is consistent with previously published structures of Abeta 40 fibrils. Fibrillar oligomers show similar pattern consistent with our hypothesis that they represent fragments of protofibrils. However, prefibrillar oligomers show lower stability towards denaturation and more hydrophobic environment throughout the 15-35 region of the peptide. Distinct conformational properties of prefibrillar oligomers may explain their differential recognition by conformational antibodies and serve as a basis for their neurotoxicity.
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Shared resource to develop tools and reagents to study structural polymorphisms in Abeta amyloid aggregates in AD
  • 批准号:
    10706566
  • 项目类别:
  • 资助金额:
    $108.96万
  • 财政年份:
    2022
  • 负责人:
    Charles G. Glabe
  • 依托单位:
Shared resource to develop tools and reagents to study structural polymorphisms in Abeta amyloid aggregates in AD
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    10549101
  • 项目类别:
  • 资助金额:
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  • 财政年份:
    2022
  • 负责人:
    Charles G. Glabe
  • 依托单位:
Temporal, Spatial and Cellular Dynamics of Amyloid Plaque Deposition
  • 批准号:
    10525630
  • 项目类别:
  • 资助金额:
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  • 财政年份:
    2022
  • 负责人:
    Charles G. Glabe
  • 依托单位:
Structure and conformational diversity of amyloid oligomers
  • 批准号:
    8235899
  • 项目类别:
  • 资助金额:
    $28.56万
  • 财政年份:
    2010
  • 负责人:
    Charles G. Glabe
  • 依托单位:
国内基金
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  • 项目类别:
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  • 批准年份:
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