Role of Target-derived FGFs in Maintaining and Repairing Synapses
靶标衍生的 FGF 在维持和修复突触中的作用
基本信息
- 批准号:8618387
- 负责人:
- 金额:$ 22.64万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2013
- 资助国家:美国
- 起止时间:2013-09-20 至 2016-08-31
- 项目状态:已结题
- 来源:
- 关键词:AdultAffectAgeAgingAlzheimer&aposs DiseaseAmyotrophic Lateral SclerosisAnimalsArchitectureAtrophicAxonBasal laminaBeliefBindingBinding ProteinsBiologicalBiotinBrainBrain DiseasesCaringCell NucleusCessation of lifeDataDefectDevelopmentDiseaseEmbryoEtiologyFibroblast Growth FactorFoundationsFoxesFundingFunding AgencyGoalsGovernmentGrowth FactorIndividualInjuryInstitutesLaboratoriesLeadLigandsMaintenanceMedicalMentorsMolecularMotorMotor NeuronsMotor SkillsMusMuscleMuscle FibersMyopathyNational Institute of Neurological Disorders and StrokeNerveNeurodegenerative DisordersNeuromuscular JunctionPeptidesPremature aging syndromePublishingQuality of lifeResearchResearch InstituteResearch Project GrantsResourcesRoleRunningSignal PathwaySignal TransductionSiteSkeletal MuscleSpinalSynapsesSystemTestingTherapeuticTrainingVirginiaage relatedcareerdesignexperienceglycosylationkeratinocyte growth factormembermotor deficitmouse modelmuscle agingneuron lossnew therapeutic targetnormal agingnoveloverexpressionplanetary Atmospherepresynapticpreventprofessorpublic health relevancereinnervationrepairedresearch studyresponseskillsstemtherapeutic developmenttrafficking
项目摘要
Project Summary/Abstract
I am a tenure-track assistant professor at the Virginia Tech Carilion Research Institute.
The interdisciplinary, interactive, collegial and nurturing atmosphere at the institute is truly
conducive for developing a successful research and academic career. To help with my career
goals, I have assembled an exceptional team of mentors, with Dr. Michael Friedlander (at
VTCRI) serving as a mentor and Dr. Kenneth Fischbeck (at NINDS) and Dr. Michael Fox (at
VTCRI) serving as co-mentors. In the short-term, I will obtain further training, acquire new skills
and the experience needed to successfully run a team-driven research project and compete for
independent sources of funding, including an R01. These experiences will provide me with the
foundation necessary to obtain tenure and run a highly successful and well-funded laboratory.
In my laboratory, I will seek to discover and manipulate molecules that act to maintain
synapses, and thereby prevent the decline of motor skills that occur with normal aging and in
blunting the effects of a multitude of age-related neurodegenerative diseases. In this proposal, I
hypothesize that maintaining the normal function of the neuromuscular junction (NMJ), a large
and experimentally accessible synapse formed between motor neurons and muscles fibers,
could be sufficient to slow or prevent the erosion of motor skills caused by aging and
amyotrophic lateral sclerosis (ALS). This hypothesis stems from the fact that deleterious
changes at the NMJ appears to precede death of motor neurons and atrophy of muscle fibers
during the progression of normal aging and ALS. In this regard, I have gathered preliminary
data suggesting that three members of the fibroblast growth factor (FGF) signaling pathway,
FGF-7/10/22, and a FGF-binding protein (FGFBP1) could be promising candidate molecules for
protecting NMJs from insults emanating from normal aging and ALS. In mice, deletion of FGF-
22 results in premature aging of the NMJ. It also delays reinnervation of skeletal muscles after
injury. Similarly, a reduction in FGFBP1 delays reinnervation of skeletal muscles. Thus, these
results suggest that FGF-22 and FGFBP1 could function to repair the NMJ. In this project, my
goal is to investigate the function of these growth factors in aging NMJs and in the initiation and
progression of ALS. In addition to the training opportunities, the proposed experiments could
lead to new therapeutic targets and approaches for protecting the motor system.
项目总结/文摘
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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Gregorio Valdez其他文献
Gregorio Valdez的其他文献
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Role of Target-derived FGFs in Maintaining and Repairing Synapses
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Role of Target-derived FGFs in Maintaining and Repairing Synapses
靶标衍生的 FGF 在维持和修复突触中的作用
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