Neuroprotection Mechanism for Photoreceptors
光感受器的神经保护机制
基本信息
- 批准号:10006824
- 负责人:
- 金额:$ 42.27万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-09-30 至 2023-06-30
- 项目状态:已结题
- 来源:
- 关键词:1p36AddressAdultAffectAge related macular degenerationBindingBiochemicalBiologicalBiological AvailabilityBlindnessCell DeathCell physiologyCell surfaceCellsCellular biologyChromosomesDefectEtiologyEventEyeFailureFamily memberFoundationsFutureGRB14 geneGene ExpressionGoalsGrowthGrowth FactorHalf-LifeHumanInsulin-Like Growth Factor IInsulin-Like Growth-Factor-Binding ProteinsInsulin-Like-Growth Factor I ReceptorKnock-outKnockout MiceLaboratoriesLeadLeber&aposs amaurosisLengthLigandsLightLiteratureLiverMaintenanceMediatingMental RetardationMethodsMicrocephalyMitochondriaMitoticMolecularMuller&aposs cellMusMutationNucleotide BiosynthesisOutcomePTK6 genePathway interactionsPatientsPharmacologyPharmacotherapyPhosphoric Monoester HydrolasesPhosphorylationPhotoreceptorsProcessPropertyProtein BiosynthesisProtein DephosphorylationProtein InhibitionProtein Tyrosine KinaseProtein phosphataseProteinsReceptor ActivationReceptor InhibitionReceptor SignalingRegulationReportingResearchRetinaRetinal ConeRetinal DegenerationRetinal DiseasesRetinitis PigmentosaRodRoleSignal PathwaySignal TransductionSignaling MoleculeSourceStressStructureTestingTissuesUp-RegulationUsher SyndromeVisionWorkage relatedblindcell growth regulationcongenital deafnessdeafnessdisease phenotypeearly onsetextracellularinnovationinorganic phosphateinsulin regulationlipid biosynthesisneoplastic cellneuroprotectionneurotrophic factornovelphotoreceptor degenerationpostnatalpreservationpreventprotein activationprotein tyrosine phosphatase 1Breceptorreceptor functionreceptor-mediated signalingresponseretinal rodssolutetranslational impact
项目摘要
PROJECT SUMMARY/ABSTRACT
Signal transduction occurs when an extracellular signaling molecule activates a specific receptor located on
the cell surface or inside the cell. In turn, this receptor triggers a biochemical chain of events inside the cell,
creating a response. The signaling network mediated by insulin-like growth factor 1 (IGF-1) receptor is
fundamentally important for the regulation of a number of cellular functions, including the neuroprotection of
post-mitotic cells. The specific objectives of this application are to investigate the mechanism of IGF-1R-
mediated signaling in both rod and cone photoreceptors, and the regulation of the cellular processes required
to promote and sustain photoreceptor functionality and viability.
The research strategy outlined in this proposal is built upon the recently uncovered function of IGF-1R in
photoreceptor neuroprotection, and a fundamental property of IGF-1R in many other cell tissues. The study
proposed herein will define how IGF-1R regulates photoreceptor functions. Using genetically modified mice
and pharmacological agents, we have identified changes in cellular signaling and gene expression in the
retina. We have identified several activators and negative regulators of IGF-1R signaling in the retina, and
have developed methods for manipulating IGF-1R activation to detect the impact on photoreceptor functions.
We will use these methods to determine how IGF-1R signaling regulates photoreceptor neuroprotection and
other cellular functions. We will study the source of IGF-1 to activate IGF-1R and the consequence of its
absence in rods (Aim 1). We will test the mechanisms of IGF-1R activation and deactivation in the retina (Aim
2).
Successful completion of our studies could benefit millions of people who are blind from rod and cone cell loss.
Our new and innovative approaches will facilitate future translational application of our work, with the goal of
applying our findings to the treatment of human retinal degenerations. Elucidating these mechanisms is critical
to advancing our understanding of basic photoreceptor cell biology and pathobiological mechanisms underlying
the photoreceptor degeneration that is frequently associated with defects in anabolic processes.
项目总结/摘要
当细胞外信号分子激活位于细胞膜上的特定受体时,
细胞表面或细胞内部。反过来,这种受体在细胞内触发了一系列生化事件,
创建一个响应。胰岛素样生长因子1(IGF-1)受体介导的信号网络是
对于调节许多细胞功能至关重要,包括神经保护,
有丝分裂后的细胞本申请的具体目的是研究IGF-1 R-1的作用机制。
在视杆和视锥光感受器中介导的信号传导,以及所需的细胞过程的调节,
以促进和维持光感受器的功能和活力。
该提案中概述的研究策略是建立在最近发现的IGF-1 R在
光感受器神经保护和IGF-1 R在许多其他细胞组织中的基本特性。研究
本文提出的将定义IGF-1 R如何调节光感受器功能。使用转基因小鼠
和药理学试剂,我们已经确定了细胞信号传导和基因表达的变化,
视网膜。我们已经鉴定了视网膜中IGF-1 R信号传导的几种激活剂和负调节剂,
已经开发了操纵IGF-1 R激活以检测对感光器功能的影响的方法。
我们将使用这些方法来确定IGF-1 R信号传导如何调节感光细胞神经保护,
其他细胞功能。我们将研究IGF-1激活IGF-1 R的来源及其影响
棒中不存在(目标1)。我们将测试IGF-1 R在视网膜中激活和失活的机制(目的
2)的情况。
成功完成我们的研究可以使数百万因视杆细胞和视锥细胞丢失而失明的人受益。
我们的创新方法将促进我们工作的未来转化应用,目标是
将我们的发现应用于人类视网膜变性的治疗。阐明这些机制至关重要
促进我们对感光细胞生物学和病理生物学机制的理解,
通常与合成代谢过程中的缺陷有关的光感受器退化。
项目成果
期刊论文数量(0)
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Raju VS Rajala其他文献
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{{ truncateString('Raju VS Rajala', 18)}}的其他基金
Regulators of Photoreceptor Aerobic Glycolysis in Retinal Health and Disease
视网膜健康和疾病中光感受器有氧糖酵解的调节因子
- 批准号:
10717825 - 财政年份:2023
- 资助金额:
$ 42.27万 - 项目类别:
Mechanistic studies on obesity-deteriorated glucose and lipid metabolisms
肥胖导致糖脂代谢恶化的机制研究
- 批准号:
8874215 - 财政年份:2013
- 资助金额:
$ 42.27万 - 项目类别:
COBRE: INSULIN RECEPTOR SIGNALING IN DIABETIC RETINOPATHY
COBRE:糖尿病视网膜病变中的胰岛素受体信号传导
- 批准号:
7720534 - 财政年份:2008
- 资助金额:
$ 42.27万 - 项目类别:
COBRE: INSULIN RECEPTOR SIGNALING IN DIABETIC RETINOPATHY
COBRE:糖尿病视网膜病变中的胰岛素受体信号传导
- 批准号:
7610500 - 财政年份:2007
- 资助金额:
$ 42.27万 - 项目类别:
COBRE: INSULIN RECEPTOR SIGNALING IN RETINA
COBRE:视网膜中的胰岛素受体信号传导
- 批准号:
7381939 - 财政年份:2006
- 资助金额:
$ 42.27万 - 项目类别:
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