Cell Signaling and Neurodegeneration
细胞信号传导和神经变性
基本信息
- 批准号:7225232
- 负责人:
- 金额:$ 42.6万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2003
- 资助国家:美国
- 起止时间:2003-08-15 至 2008-04-30
- 项目状态:已结题
- 来源:
- 关键词:AlanineBiochemicalBiologicalDataDepositionDiseaseEnzymesGlutamineGlycogen Synthase Kinase 3GoalsIn VitroLithiumMediatingMusNerve DegenerationNeurodegenerative DisordersPathogenesisPhosphorylationPhosphotransferasesPlayPositioning AttributeProcessProteinsPurkinje CellsResearchRoleSeriesSerineSignal PathwaySignal TransductionSiteSpinocerebellar AtaxiasTherapeuticTransgenic MiceType 1 Spinocerebellar AtaxiaVariantWorkataxin-1drug discoveryin vivoinhibitor/antagonistintracellular protein transportmutantprotein localization locationresearch studytherapeutic targettissue culture
项目摘要
DESCRIPTION (provided by applicant): Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disorder caused by the expansion of a glutamine repeat within the SCA1-encoded protein ataxin-1. Previous work has shown that the subcellular deposition and localization of mutant ataxin-1 plays a critical role in the pathogenesis of SCA1. A key player in numerous cell-signaling pathways, many associated with neurodegeneration, is the enzyme glycogen synthase kinase 3 (GSK3). Our results indicate that serines 776 and 780 of ataxin-1 play a role in the subcellular localization of this protein, perhaps via their phosphorylation by GSK3b. Thus, the goal of the research described below is to determine whether cell-signaling pathways acting through these serines of ataxin-1 are biologically relevant GSK3b has recently emerged as a key target in drug discovery. If it proves to be the case that SCA1 pathogenesis is associated with increased levels of GSK3b activity, GSK3b inhibitors might have a therapeutic role in SCA1.
描述(由申请方提供):脊髓小脑共济失调1型(SCA 1)是一种常染色体显性遗传神经退行性疾病,由SCA 1编码的蛋白共济失调蛋白-1内谷氨酰胺重复序列扩增引起。先前的研究表明,突变型ataxin-1的亚细胞沉积和定位在SCA 1的发病机制中起着至关重要的作用。糖原合成酶激酶3(GSK 3)是许多细胞信号传导途径中的一个关键参与者,其中许多与神经变性有关。我们的研究结果表明,ataxin-1的丝氨酸776和780在这种蛋白质的亚细胞定位中发挥作用,可能是通过它们被GSK 3b磷酸化。因此,下面描述的研究的目标是确定通过这些共济失调蛋白-1丝氨酸起作用的细胞信号传导途径是否与生物学相关,GSK 3b最近已成为药物发现的关键靶点。如果证实SCA 1发病机制与GSK 3b活性水平升高相关,则GSK 3b抑制剂可能在SCA 1中具有治疗作用。
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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Harry T. Orr其他文献
Report of the Second International Workshop on Human Chromosome 6.
第二届人类 6 号染色体国际研讨会报告。
- DOI:
- 发表时间:
1994 - 期刊:
- 影响因子:4.4
- 作者:
A. Volz;John M Boyle;H. M. Cann;Robert W. Cottingham;Harry T. Orr;Andreas Ziegler - 通讯作者:
Andreas Ziegler
An expanded polyglutamine in ATAXIN1 results in a loss-of-function that exacerbates severity of Multiple Sclerosis in an EAE mouse model
- DOI:
10.1186/s12974-025-03450-2 - 发表时间:
2025-04-30 - 期刊:
- 影响因子:10.100
- 作者:
Gourango Talukdar;Lisa Duvick;Praseuth Yang;Brennon O’Callaghan;Gavin J. Fuchs;Marija Cvetanovic;Harry T. Orr - 通讯作者:
Harry T. Orr
Stephen T. Warren, Ph.D. (1953-2021): A remembrance.
斯蒂芬·沃伦博士
- DOI:
10.1016/j.ajhg.2021.12.005 - 发表时间:
2022 - 期刊:
- 影响因子:9.8
- 作者:
David L. Nelson;Janelle Clark;Kathryn Garber;Thomas Glover;Terry J. Hassold;Peng Jin;Harry T. Orr;Stephanie L. Sherman;H. Zoghbi;Karen L. Warren - 通讯作者:
Karen L. Warren
Neuron protection agency
神经元保护机构
- DOI:
10.1038/431747a - 发表时间:
2004-10-13 - 期刊:
- 影响因子:48.500
- 作者:
Harry T. Orr - 通讯作者:
Harry T. Orr
Comparison of amino acid sequences of two human histocompatibility antigens, HLA-A2 and HLA-B7: location of putative alloantigenic sites.
两种人类组织相容性抗原 HLA-A2 和 HLA-B7 的氨基酸序列的比较:推定同种异体抗原位点的位置。
- DOI:
- 发表时间:
1979 - 期刊:
- 影响因子:11.1
- 作者:
Harry T. Orr;J. A. L. D. Castro;Peter Parham;H. Ploegh;J. L. Strominger - 通讯作者:
J. L. Strominger
Harry T. Orr的其他文献
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{{ truncateString('Harry T. Orr', 18)}}的其他基金
Molecular genetics of neurodegenerative pathogenic and protective pathways: The SCA1 perspective
神经退行性病变致病和保护途径的分子遗传学:SCA1 视角
- 批准号:
10450471 - 财政年份:2022
- 资助金额:
$ 42.6万 - 项目类别:
Molecular genetics of neurodegenerative pathogenic and protective pathways: The SCA1 perspective
神经退行性病变致病和保护途径的分子遗传学:SCA1 视角
- 批准号:
10614029 - 财政年份:2022
- 资助金额:
$ 42.6万 - 项目类别:
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