Probing Neurodegeneration with Drosophila

用果蝇探测神经退行性变

基本信息

  • 批准号:
    7625349
  • 负责人:
  • 金额:
    $ 38.38万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2001
  • 资助国家:
    美国
  • 起止时间:
    2001-07-01 至 2009-06-30
  • 项目状态:
    已结题

项目摘要

The ultimate goal of this project is to identify molecular mechanisms of pathogenesis and potential therapeutic targets that are common to Spinocerebellar ataxias (SCAs). These are a group ~30 genetically heterogeneous neurodegenerative disorders that share neuropathological and clinical features such as atrophy of the cerebellum and loss of motor coordination and balance. Recent data points to unsuspected links among inherited ataxias. First, a proteinprotein- interaction network for inherited ataxias revealed that many ataxia-causing proteins share interacting partners. Second, dAtaxin-2 (an orthologue of the protein responsible for SCA2) is a major modifier of Ataxin-1[82Q]-induced neurotoxicity in a Drosophila model of SCA1. Together, these observations suggest that SCAs, and perhaps other inherited ataxias may share molecular mechanisms of pathogenesis in addition to similar neuropathology and clinical features. This hypothesis predicts that SCAs have common genetic modifiers and potential therapeutic targets that remain unknown. Testing this hypothesis requires a thorough comparison of genetic modifiers and mechanisms of pathogenesis among different inherited ataxias. A genetic approach will be employed to identify modifiers of neurotoxicity caused by expanded Ataxin-1, Ataxin-2 and Ataxin-7, the proteins responsible for SCA1, SCA2 an SCA7. The work proposed here will address the following specific aims: 1) To investigate the molecular mechanisms by which partial loss of dAtaxin-2 function suppresses Ataxin-1[82Q]-induced neurodegeneration. 2) To screen the ataxia interactome for genetic modifiers of Ataxin-1[82Q]-induced neurotoxicity. 3) To test the Ataxin-1[82Q] genetic modifiers and the ataxia interactome in Drosophila models of SCA2 and SCA7. 4) To investigate selected genetic modifiers that are common to the Drosophila SCA models. These comparative studies are impractical with mammalian models, but feasible using Drosophila. The suppressors of neurodegeneration identified as a result of this work may directly point to specific therapeutic targets. These basic studies are prerequisite to developing therapies for these neurodegenerative disorders for which there are no effective treatments.
这个项目的最终目标是确定的分子机制

项目成果

期刊论文数量(0)
专著数量(0)
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专利数量(0)

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Juan Botas其他文献

Juan Botas的其他文献

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{{ truncateString('Juan Botas', 18)}}的其他基金

Functional Dissection of Alzheimer's Disease Networks in Drosophila: from Association to Causal Modulators of Age-Dependent Neurodegeration
果蝇阿尔茨海默病网络的功能剖析:从年龄依赖性神经变性的关联到因果调节因子
  • 批准号:
    10228292
  • 财政年份:
    2017
  • 资助金额:
    $ 38.38万
  • 项目类别:
Neurodegeneration with Drosophila
果蝇神经变性
  • 批准号:
    6540512
  • 财政年份:
    2001
  • 资助金额:
    $ 38.38万
  • 项目类别:
Neurodegeneration with Drosophila
果蝇神经变性
  • 批准号:
    6769927
  • 财政年份:
    2001
  • 资助金额:
    $ 38.38万
  • 项目类别:
Probing Neurodegeneration with Drosophila
用果蝇探测神经退行性变
  • 批准号:
    8098002
  • 财政年份:
    2001
  • 资助金额:
    $ 38.38万
  • 项目类别:
Neurodegeneration with Drosophila
果蝇神经变性
  • 批准号:
    6365396
  • 财政年份:
    2001
  • 资助金额:
    $ 38.38万
  • 项目类别:
Probing Neurodegeneration with Drosophila
用果蝇探测神经退行性变
  • 批准号:
    8051741
  • 财政年份:
    2001
  • 资助金额:
    $ 38.38万
  • 项目类别:
Neurodegeneration with Drosophila
果蝇神经变性
  • 批准号:
    6484917
  • 财政年份:
    2001
  • 资助金额:
    $ 38.38万
  • 项目类别:
Probing Neurodegeneration with Drosophila
用果蝇探测神经退行性变
  • 批准号:
    8289572
  • 财政年份:
    2001
  • 资助金额:
    $ 38.38万
  • 项目类别:
Neurodegeneration with Drosophila
果蝇神经变性
  • 批准号:
    6612622
  • 财政年份:
    2001
  • 资助金额:
    $ 38.38万
  • 项目类别:
Neurodegeneration with Drosophila
果蝇神经变性
  • 批准号:
    6556320
  • 财政年份:
    2001
  • 资助金额:
    $ 38.38万
  • 项目类别:

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