Elucidating Neuron-Intrinsic Molecular Mechanisms of Optic Nerve Regeneration
阐明视神经再生的神经元固有分子机制
基本信息
- 批准号:9316634
- 负责人:
- 金额:$ 38.93万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-12-01 至 2019-07-31
- 项目状态:已结题
- 来源:
- 关键词:AdultAffinity ChromatographyAnatomyAxonCell ProliferationComplexCorticospinal TractsDevelopmentDiseaseDrosophila genusElementsFMR1FRAP1 geneFailureGrowthIndividualInjuryIntrinsic factorLinkMediatingMetabolic DiseasesMethodsMicroarray AnalysisModelingMolecularMusNatural regenerationNerve CrushNeuraxisNeurofibromatosis 1NeuronsNodalOptic NerveOptic Nerve InjuriesPDPK1 genePTEN genePathway interactionsPatientsPhosphorylationPositioning AttributeProtein BiosynthesisProto-Oncogene Proteins c-aktRecovery of FunctionRetinal Ganglion CellsRibosomesRoleSensorySignal TransductionSignaling MoleculeTestingTherapeuticTranscriptTranslatingTranslationsTuberous SclerosisTumor Suppressor ProteinsUp-Regulationaxon growthaxon injuryaxon regenerationcentral nervous system injuryexperimental studyextracellulargenetic manipulationin vivoinhibitor/antagonistmutantnerve injurynervous system disordernovelnovel therapeutic interventionoptic nerve disorderoptic nerve regenerationpublic health relevanceregenerativeregenerative therapyrelating to nervous systemrepairedscreeningtherapeutic targettumor
项目摘要
DESCRIPTION (provided by applicant): Injuries of mature central nervous system (CNS) axons result in loss of vital functions due to the failure of CNS axons regeneration. Neutralizing extracellular inhibitory molecules yields only limited regeneration or functional recovery in vivo,
suggesting a critical role for neuron-intrinsic factors. As it has become apparent that the PTEN/mTOR pathway is critical for CNS axon regeneration, understanding the regrowth control of this pathway represents the first step toward developing novel therapeutic approaches to neural injury. Unfortunately, mTOR over-activity can result in tumor formation, metabolic diseases, and neurological disorders. It is therefore critically important to identify the specific
downstream effectors by which PTEN/mTOR promotes axon regeneration, and to isolate them from other targets that mediate mTOR's deleterious effects. Using the anatomical and technical advantages of retinal ganglion cell and optic nerve as a CNS injury model, we have identified crucial regulators of axon growth, and are now ideally positioned to elucidate the downstream mechanisms by which PTEN/mTOR stimulates regeneration in mature CNS axons and identify translational targets of PTEN/mTOR govern adult CNS axon regeneration. These effectors are ideal therapeutic targets to promote regeneration in CNS injury and diseases, which can be selectively activated without activating other, potentially harmful pathways, thus to assist in safely translating our findings into novel neural repair treatments to preserve vital functions in patients with CNS injuries.
描述(由申请人提供):由于CNS轴突再生失败,成熟中枢神经系统(CNS)轴突损伤导致生命功能丧失。中和细胞外抑制分子在体内仅产生有限的再生或功能恢复,
提示神经元内源性因子的关键作用。由于已经变得明显的是,PTEN/mTOR通路对于CNS轴突再生是至关重要的,理解该通路的再生控制代表了开发神经损伤的新治疗方法的第一步。不幸的是,mTOR过度活性可导致肿瘤形成、代谢疾病和神经系统疾病。因此,至关重要的是,
下游效应物,通过其PTEN/mTOR促进轴突再生,并将它们与介导mTOR有害作用的其他靶标分离。利用视网膜神经节细胞和视神经作为CNS损伤模型的解剖学和技术优势,我们已经确定了轴突生长的关键调节因子,并且现在理想地定位于阐明PTEN/mTOR刺激成熟CNS轴突再生的下游机制,并确定PTEN/mTOR的翻译靶点支配成人CNS轴突再生。这些效应物是促进CNS损伤和疾病再生的理想治疗靶点,可以选择性激活而不激活其他潜在有害的途径,从而有助于将我们的发现安全地转化为新型神经修复治疗,以保护CNS损伤患者的重要功能。
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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Yang Hu其他文献
Yang Hu的其他文献
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{{ truncateString('Yang Hu', 18)}}的其他基金
In Vivo Function and Metabolism Evaluation of Glaucomatous RGCs by Two-Photon Scanning Laser Ophthalmology
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Mechanisms of peroxisome proliferator-activated receptor-alpha regulation in peridontitis
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10915090 - 财政年份:2023
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$ 38.93万 - 项目类别:
Optineurin dysfunction induces neurodegeneration in normal tension glaucoma by a novel molecular mechanism
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10372873 - 财政年份:2022
- 资助金额:
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Optineurin dysfunction induces neurodegeneration in normal tension glaucoma by a novel molecular mechanism
Optineurin功能障碍通过一种新的分子机制诱导正常眼压青光眼的神经变性
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10557146 - 财政年份:2022
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Neuroprotection by Modulating ER Stress in Glaucoma
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10390110 - 财政年份:2021
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Pathogenic role of peroxisome proliferator-activated receptor alpha in periodontitis
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Developing Novel Neuroprotective Strategies for EAE/Optic Neuritis
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10200056 - 财政年份:2018
- 资助金额:
$ 38.93万 - 项目类别:
Neuroprotection by Modulating ER Stress in Glaucoma
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9430478 - 财政年份:2017
- 资助金额:
$ 38.93万 - 项目类别:
Elucidating Neuron-Intrinsic Molecular Mechanisms of Optic Nerve Regeneration
阐明视神经再生的神经元固有分子机制
- 批准号:
9438581 - 财政年份:2016
- 资助金额:
$ 38.93万 - 项目类别:
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