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
- 来源:
- 关键词:AddressAtaxiaAtrophicBehavioralBiological AssayCerebellumCharacteristicsClinicalComparative StudyDataDiseaseDrosophila genusElementsEquilibriumEyeGeneticGenetic ScreeningGenomeGoalsInheritedLY6E geneLinkModelingMolecularMotorNerve DegenerationNeurodegenerative DisordersNeuromuscular DiseasesPathogenesisPathologyPeripheral Nervous SystemPhenotypeProteinsPublishingSCA2 proteinSCA7 proteinSensorySpinocerebellar AtaxiasTestingType 1 Spinocerebellar AtaxiaValidationWorkataxin-1basecell typecomparativeneuropathologyneurotoxicitynovelprotein protein interactiontherapeutic targetunpublished works
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)
科研奖励数量(0)
会议论文数量(0)
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:
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