RNA editing of AMPA receptor subunit GluR2 in ischemia
缺血中 AMPA 受体亚基 GluR2 的 RNA 编辑
基本信息
- 批准号:7766886
- 负责人:
- 金额:$ 31.02万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2006
- 资助国家:美国
- 起止时间:2006-05-15 至 2011-01-31
- 项目状态:已结题
- 来源:
- 关键词:AMPA ReceptorsAddressAdenosineAreaCause of DeathCyclic AMP-Responsive DNA-Binding ProteinCytoplasmic GranulesDRADA2b proteinDataDefectDeveloped CountriesDeveloping CountriesDiseaseEnzymesEpileptogenesisGene ExpressionGene SilencingGenerationsGenesGluR2 subunit AMPA receptorGlutamate ReceptorGlutamatesHippocampus (Brain)IndividualIschemiaIschemic Neuronal InjuryIschemic StrokeLeadN-Methyl-D-Aspartate ReceptorsNerve DegenerationNeuronal InjuryNeuronsNuclearPatternPermeabilityPhysiologicalPredispositionPropertyProsencephalonRNARNA EditingRattusReportingResearch PersonnelResistanceSeizuresSiteSmall Interfering RNASynapsesWorkdentate gyrusdesensitizationdsRNA adenosine deaminasehippocampal pyramidal neuronneuron lossneuronal survivalresearch studyrestorationtranscription factorvector
项目摘要
Ischemic stroke is the third leading cause of death in developed countries. A critical feature of the disease is
a highly selective pattern of neuronal loss; certain identifiable subsets of neurons, particularly CA1
pyramidal neurons in the hippocampus, are severely damaged while others remain intact. A step in this
selective neuronal injury involves Ca2+ entry through Ca2+-permeable AMPA receptor channels. AMPA
receptors are a major subtype of glutamate receptors (GluRs) that are assembled from GluR1-4 subunits.
Ca2+ permeability of the channels is dominated by GluR2 RNA editing at the Q/R site; edited GluR2(R)
subunits form Ca2+-impermeable channels, whereas unedited GluR2(Q) channels allow Ca2+ entry. In
most CA1 neurons, AMPA receptor channels contain GluR2(R), and thus are impermeable to Ca2+ flow.
Recently, we have identified that transient forebrain ischemia selectively disrupts GluR2 Q/R site editing and
hence induces injurious Ca2+ entry through AMPA receptor channels into vulnerable CA1 neurons. We
have also shown that impaired GluR2 Q/R site editing is closely correlated with reduced expression of
ADAR2 (short for adenosine deaminase acting on RNA) gene, a nuclear enzyme responsible for GluR2 Q/R
site editing. We thus hypothesize that reduced expression of ADAR2 gene is responsible for the impaired
GluR2 Q/R site editing. To address this hypothesis directly, we will determine if restoration of ADAR2 gene
expression rescues GluR2 Q/R site editing and in turn blocks Ca2+ permeability of AMPA receptor
channels, leading to the survival of vulnerable neurons in the post-ischemic rats. Overall, this project will
have two specific aims:
Specific Aim 1: To determine whether restoration of ADAR2 gene expression blocks Ca2+ entry through
AMPA receptor channels and rescues vulnerable neurons in the post-ischemic rats.
Specific Aim 2: To determine if generation of stable ADAR2 gene silencing induces degeneration of
ischemia-insensitive neurons, and if degeneration of ADAR2-deficient neurons results from RNA editing
deficits of one or more glutamate receptor subunits.
Together, this project will identify that ADAR2-dependent GluR2 Q/R site editing determines vulnerability of
neurons to ischemia. Thus, this work will define a promising target for stoke therapy.
缺血性中风是发达国家第三大死亡原因。这种疾病的一个关键特征是
项目成果
期刊论文数量(0)
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{{ truncateString('YOUMING LU', 18)}}的其他基金
DAPK1 regulation of NMDA receptors in ischemic neuronal death
DAPK1 对 NMDA 受体在缺血性神经元死亡中的调节
- 批准号:
7675965 - 财政年份:2008
- 资助金额:
$ 31.02万 - 项目类别:
DAPK1 regulation of NMDA receptors in ischemic neuronal death
DAPK1 对 NMDA 受体在缺血性神经元死亡中的调节
- 批准号:
7888146 - 财政年份:2008
- 资助金额:
$ 31.02万 - 项目类别:
DAPK1 regulation of NMDA receptors in ischemic neuronal death
DAPK1 对 NMDA 受体在缺血性神经元死亡中的调节
- 批准号:
7522367 - 财政年份:2008
- 资助金额:
$ 31.02万 - 项目类别:
DAPK1 regulation of NMDA receptors in ischemic neuronal death
DAPK1 对 NMDA 受体在缺血性神经元死亡中的调节
- 批准号:
8142986 - 财政年份:2008
- 资助金额:
$ 31.02万 - 项目类别:
DAPK1 regulation of NMDA receptors in ischemic neuronal death
DAPK1 对 NMDA 受体在缺血性神经元死亡中的调节
- 批准号:
7786536 - 财政年份:2008
- 资助金额:
$ 31.02万 - 项目类别:
DAPK1 regulation of NMDA receptors in ischemic neuronal death
DAPK1 对 NMDA 受体在缺血性神经元死亡中的调节
- 批准号:
8117740 - 财政年份:2008
- 资助金额:
$ 31.02万 - 项目类别:
RNA editing of AMPA receptor subunit GluR2 in ischemia
缺血中 AMPA 受体亚基 GluR2 的 RNA 编辑
- 批准号:
7760657 - 财政年份:2006
- 资助金额:
$ 31.02万 - 项目类别:
RNA editing of AMPA receptor subunit GluR2 in ischemia
缺血中 AMPA 受体亚基 GluR2 的 RNA 编辑
- 批准号:
7140760 - 财政年份:2006
- 资助金额:
$ 31.02万 - 项目类别:
RNA editing of AMPA receptor subunit GluR2 in ischemia
缺血中 AMPA 受体亚基 GluR2 的 RNA 编辑
- 批准号:
7233658 - 财政年份:2006
- 资助金额:
$ 31.02万 - 项目类别:
RNA editing of AMPA receptor subunit GluR2 in ischemia
缺血中 AMPA 受体亚基 GluR2 的 RNA 编辑
- 批准号:
7354764 - 财政年份:2006
- 资助金额:
$ 31.02万 - 项目类别:
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