CHARACTERIZATION OF POLYGLUTAMINE AGGREGATES BY MASS SPECTROMETRY
通过质谱法表征聚谷氨酰胺聚集体
基本信息
- 批准号:8170904
- 负责人:
- 金额:$ 3.37万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2010
- 资助国家:美国
- 起止时间:2010-06-01 至 2011-05-31
- 项目状态:已结题
- 来源:
- 关键词:AffectCell DeathCellsComplexComputer Retrieval of Information on Scientific Projects DatabaseDataDiseaseDoctor of PhilosophyFundingGrantHumanHuntington proteinInheritedInstitutionJournalsLeadManuscriptsMass Spectrum AnalysisMethodsModelingNeurodegenerative DisordersNeuronsPhaseProceduresProtein IsoformsProteinsProteomicsPublishingResearchResearch PersonnelResourcesSourceUnited States National Institutes of HealthYeastscrosslinkmutantnovelpolyglutamineprotein aggregateprotein protein interactionresearch studyspatial relationship
项目摘要
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.
Polyglutamine diseases are inherited neurodegenerative diseases caused by the expansion of polyglutamine tract in the disease-causing mutant proteins. A unifying pathological feature of polyglutamine disorders is the presence of microscopically discernible intracellular inclusions in the affected neurons. It has been proposed that expanded polyglutamine tract formed-aggregates participate in inappropriate protein-protein interactions that lead to cell death. To date, there is still no reliable method to isolate highly purified aggregates which are usually morphologically heterogeneous. We have developed a new purification method and the proteomics procedure was carried out to analyze the aggregate-interacting proteins by mass spectrometry. Mass spectrometry provides a powerful and direct analysis of aggregate proteins in tiny quantities and will help us understand the nativity of aggregates in the polyglutamine disorders. We have obtained mass spectral data that indicates the presence of several expected proteins in the aggregate and others that would not have been easily predicted. Immunochemical approaches have confirmed these aggregate interacting proteins. A manuscript describing our novel purification method was recently published. Recent experiments have provided evidence that the yeast cells form aggresomes from some isoforms of the Huntington proteins; this is the first indication that aggresomes can form in yeast. The manuscript describing the identification of proteins that are required for aggresome formation and presenting our new model for aggresome formation has been published in FASEB journal. Extensive details are included in the PhD thesis of Y. Wang, completed in June 2008. In the current phase of the research, human cells are being employed. The components of the complex are again being identified using proteomic approaches. In addition, their spatial relationships to one another will be probed using the top-down crosslinking methods being developed within a TRD project.
这个子项目是众多研究子项目之一
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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Michael Y Sherman其他文献
Michael Y Sherman的其他文献
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{{ truncateString('Michael Y Sherman', 18)}}的其他基金
CHARACTERIZATION OF HUNTINGTON AND PARKINSON AGGREGATES BY MASS SPECTROMETRY
通过质谱法表征亨廷顿和帕金森聚集体
- 批准号:
8365536 - 财政年份:2011
- 资助金额:
$ 3.37万 - 项目类别:
CHARACTERIZATION OF POLYGLUTAMINE AGGREGATES BY MASS SPECTROMETRY
通过质谱法表征聚谷氨酰胺聚集体
- 批准号:
7955936 - 财政年份:2009
- 资助金额:
$ 3.37万 - 项目类别:
Suppression of the heat shock response in aging and neurodegeneration
抑制衰老和神经退行性疾病中的热休克反应
- 批准号:
7512138 - 财政年份:2008
- 资助金额:
$ 3.37万 - 项目类别:
CHARACTERIZATION OF POLYGLUTAMINE AGGREGATES BY MASS SPECTROMETRY
通过质谱法表征聚谷氨酰胺聚集体
- 批准号:
7723036 - 财政年份:2008
- 资助金额:
$ 3.37万 - 项目类别:
Suppression of the heat shock response in aging and neurodegeneration
抑制衰老和神经退行性疾病中的热休克反应
- 批准号:
7668382 - 财政年份:2008
- 资助金额:
$ 3.37万 - 项目类别:
CHARACTERIZATION OF POLYGLUTAMINE AGGREGATES BY MASS SPECTROMETRY
通过质谱法表征聚谷氨酰胺聚集体
- 批准号:
7602030 - 财政年份:2007
- 资助金额:
$ 3.37万 - 项目类别:
Cellular Mechanisms of Aggregation of Abnormal Proteins
异常蛋白质聚集的细胞机制
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8034757 - 财政年份:2004
- 资助金额:
$ 3.37万 - 项目类别:
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