Modeling Neurofibrillary Degeneration

神经原纤维变性建模

基本信息

  • 批准号:
    7432543
  • 负责人:
  • 金额:
    $ 26.31万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2004
  • 资助国家:
    美国
  • 起止时间:
    2004-09-15 至 2010-05-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Progressive supranuclear palsy shares its defining pathologic signature, neurofibrillary tangles (NFT) consisting primarily of hyperphosphorylated tau, with numerous neurological diseases, including Alzheimer's disease, corticobasal degeneration, Pick's disease as well as frontotemporal dementia and Parkinsonism linked to chromosome 17. To improve our understanding of the mechanism underlying NFT formation and its functional impacts we have developed cellular models that produce tau filaments with morphological and biochemical characteristics of human tauopathies. The models consist of conditional transfectants generated from human neuroglioma [H4] and neuronal [BE(2)-M17D] cells in which transgenic production of wild-type or mutant tau is regulated via the TetOff inducible mechanism. Preliminary studies demonstrated that treatment of these cells with 4-hydroxynonneal (HNE), proteosomal or calpain inhibitors enhances the assembly of disulfide-linked tau aggregates. The results suggest that cellular insults such as oxidative stress and deregulation of proteases may play a role in the formation of NFT. We will employ this cellular model to uncover the molecular mechanism underlying tau aggregation induced by various insults. The Specific Aims of our proposal are: (1). To test if factors implicated in the etiology and pathogenesis of human tauopathies exacerbate tau aggregation in conditional transfectants, (2). To determine if the enhanced aggregation is associated with changes in tau solubility/partition, phosphorylation, degradation and oligomerization, (3). To investigate whether such exacerbated tau aggregation is associated with altered level or state of activation/activity of particular kinases, proteases and/or proteasomes, and (4). To study if progression of the exacerbated assembly of tau aggregates can be blocked through deregulating kinases/proteases. The results are likely to provide valuable information for a rational design of therapeutics to treat neurofibrillary degeneration.
描述(由申请人提供):

项目成果

期刊论文数量(0)
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会议论文数量(0)
专利数量(0)

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SHU-HUI C YEN其他文献

SHU-HUI C YEN的其他文献

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{{ truncateString('SHU-HUI C YEN', 18)}}的其他基金

Biochemistry and Cell Biology of alpha-Synucleinopathies
α-突触核蛋白病的生物化学和细胞生物学
  • 批准号:
    6842193
  • 财政年份:
    2004
  • 资助金额:
    $ 26.31万
  • 项目类别:
Modeling Neurofibrillary Degeneration
神经原纤维变性建模
  • 批准号:
    6866869
  • 财政年份:
    2004
  • 资助金额:
    $ 26.31万
  • 项目类别:
Modeling Neurofibrillary Degeneration
神经原纤维变性建模
  • 批准号:
    7248629
  • 财政年份:
    2004
  • 资助金额:
    $ 26.31万
  • 项目类别:
MECHANISMS OF TAU PATHOGENSIS IN A CELL MODEL OF TAUOPATHY
TAU 病变细胞模型中 TAU 发病机制
  • 批准号:
    6878765
  • 财政年份:
    2004
  • 资助金额:
    $ 26.31万
  • 项目类别:
Modeling Neurofibrillary Degeneration
神经原纤维变性建模
  • 批准号:
    7090624
  • 财政年份:
    2004
  • 资助金额:
    $ 26.31万
  • 项目类别:
Modeling Neurofibrillary Degeneration
神经原纤维变性建模
  • 批准号:
    6948775
  • 财政年份:
    2004
  • 资助金额:
    $ 26.31万
  • 项目类别:
PATHOBIOLOGY OF NEURODEGENERATIVE DISEASES LINKED TO TAU GENE MUTATIONS
与 TAU 基因突变相关的神经退行性疾病的病理学
  • 批准号:
    6338597
  • 财政年份:
    2000
  • 资助金额:
    $ 26.31万
  • 项目类别:
PATHOBIOLOGY OF NEURODEGENERATIVE DISEASES LINKED TO TAU GENE MUTATIONS
与 TAU 基因突变相关的神经退行性疾病的病理学
  • 批准号:
    6205226
  • 财政年份:
    1999
  • 资助金额:
    $ 26.31万
  • 项目类别:
AGING BRAIN--IMMUNOHISTOLOGY AND BIOCHEMISTRY
大脑老化——免疫组织学和生物化学
  • 批准号:
    2442201
  • 财政年份:
    1993
  • 资助金额:
    $ 26.31万
  • 项目类别:
AGING BRAIN--IMMUNOHISTOLOGY AND BIOCHEMISTRY
大脑老化——免疫组织学和生物化学
  • 批准号:
    3479940
  • 财政年份:
    1993
  • 资助金额:
    $ 26.31万
  • 项目类别:

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