Targeting the fibroblast growth factor binding protein-1 to slow degeneration of neuromuscular junctions
靶向成纤维细胞生长因子结合蛋白-1 减缓神经肌肉接头的退化
基本信息
- 批准号:9903183
- 负责人:
- 金额:$ 32.69万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-04-15 至 2022-03-31
- 项目状态:已结题
- 来源:
- 关键词:AffectAgeAgingAlzheimer&aposs DiseaseAmyotrophic Lateral SclerosisAxonBrainBrain DiseasesCaringCessation of lifeDataDevelopmentDiseaseDisease ProgressionEpigenetic ProcessExtracellular MatrixFGFBP1 geneFibroblast Growth FactorGoalsGrantHealthIn VitroKnock-outKnockout MiceKnowledgeLengthLigandsMeasuresMedicalMitochondriaModelingModificationMolecularMolecular ChaperonesMotorMotor NeuronsMovementMusMuscleMuscle FibersMuscular AtrophyNatural regenerationNeuromuscular JunctionOutcomeOutputPathway interactionsPhysiologicalPlayProteinsPublishingQuality of lifeRecombinant Fibroblast Growth FactorResourcesRoleSchwann CellsSignal TransductionSkeletal MuscleStructureSubcellular structureSynapsesSynaptic VesiclesSystemTestingTherapeuticTransforming Growth FactorsWestern BlottingWorkage relatedbasecholinergiccostdesignexperimental studyextracellularin vivoloss of functionmiddle agemotor deficitmotor disordermouse modelmuscle agingmuscle degenerationnormal agingprematurepreservationpreventquantumreceptorrepairedtooltranscription factortransmission processyoung adult
项目摘要
Project Summary/Abstract
The loss of motor function that occurs with aging is closely associated with adverse health
outcomes. In recent years, published findings strongly suggest that malfunction and
degeneration of the neuromuscular junction (NMJ), the synapse formed between α-motor
neurons and skeletal muscle fibers, contributes to age-related motor dysfunction. As the final
output of the somatic motor system, degeneration of the NMJ inevitably results in degeneration
of motor axons and atrophy of muscle fibers, thus affecting voluntary movement. Thus, it is
critical to identify factors that function to maintain and repair the NMJ. Using an R56 grant
provided by NIA, our lab has identified the fibroblast growth factor binding protein 1 (FGFBP1)
as a promising candidate factor secreted by muscle fibers to preserve and restore the integrity
of NMJs during aging. FGFBP1 functions to chaperone FGF ligands from the extracellular
matrix to cognate receptors. In this manner, it enhances FGF signaling. We have found that
while FGFBP1 concentrates at NMJs in young adult mice, it progressively decreases during
normal aging and in SOD1G93A mice, a mouse model for ALS. Using knockout mice, we
observed that FGFBP1 expression is required to slow aging of NMJs and motor deficits during
normal aging. Furthermore, FGFBP1 deletion in mice expressing SOD1G93A, a model for
amyotrophic lateral sclerosis (ALS), accelerates NMJ degeneration, disease progression and
death. These initial discoveries strongly suggest that preventing loss of endogenous of
FGFBP1 during aging may be sufficient to slow degeneration of NMJs, and thus preserve motor
function. To test this hypothesis, we proposed three specific aims that build on each other. In
aim 1, we test the hypothesis that motor deficits in mice deficient for FGFBP1 result from
cellular, molecular, and physiological changes at NMJs. In aim 2, we will seek to identify
molecular mechanisms that inhibit FGFBP1 expression in aging muscles. In aim 3, we will test
the hypothesis that FGFBP1 is sufficient to prevent and reverse age-related changes of NMJs.
These aims are designed to uncover the initial changes that precipitate aging of NMs, the
molecular factors that result in decreased FGFBP1 expression in aging muscle, and the
therapeutic potential of FGFBP1 in preserving NMJs and motor function.
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Gregorio Valdez其他文献
Gregorio Valdez的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Gregorio Valdez', 18)}}的其他基金
Development of a microbial-rich exposure regimen to accelerate translational research using mouse models of Alzheimer's Disease to humans.
开发富含微生物的暴露方案,以加速使用阿尔茨海默病小鼠模型对人类的转化研究。
- 批准号:
10681908 - 财政年份:2023
- 资助金额:
$ 32.69万 - 项目类别:
Role of synaptic Schwann cells in NMJ and skeletal muscle aging
突触雪旺细胞在 NMJ 和骨骼肌衰老中的作用
- 批准号:
10688321 - 财政年份:2022
- 资助金额:
$ 32.69万 - 项目类别:
Targeting the fibroblast growth factor binding protein-1 to slow degeneration of neuromuscular junctions
靶向成纤维细胞生长因子结合蛋白-1 减缓神经肌肉接头的退化
- 批准号:
9290385 - 财政年份:2017
- 资助金额:
$ 32.69万 - 项目类别:
Dysregulated cholinergic transmission contributes to aging of the lower motor system
胆碱能传输失调导致下运动系统老化
- 批准号:
9565885 - 财政年份:2017
- 资助金额:
$ 32.69万 - 项目类别:
Synaptic FGFs are required and sufficient to maintain and repair aged NMJs
突触 FGF 是维持和修复老化 NMJ 所必需的且足够的
- 批准号:
9143829 - 财政年份:2015
- 资助金额:
$ 32.69万 - 项目类别:
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
- 批准号:
8618387 - 财政年份:2013
- 资助金额:
$ 32.69万 - 项目类别:
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
- 批准号:
8738734 - 财政年份:2013
- 资助金额:
$ 32.69万 - 项目类别:
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
- 批准号:
8896083 - 财政年份:2013
- 资助金额:
$ 32.69万 - 项目类别:
Molecular basis of age-related synaptic alterations
年龄相关突触改变的分子基础
- 批准号:
7539575 - 财政年份:2008
- 资助金额:
$ 32.69万 - 项目类别:
Molecular basis of age-related synaptic alterations
年龄相关突触改变的分子基础
- 批准号:
7683976 - 财政年份:2008
- 资助金额:
$ 32.69万 - 项目类别:
相似国自然基金
靶向递送一氧化碳调控AGE-RAGE级联反应促进糖尿病创面愈合研究
- 批准号:JCZRQN202500010
- 批准年份:2025
- 资助金额:0.0 万元
- 项目类别:省市级项目
对香豆酸抑制AGE-RAGE-Ang-1通路改善海马血管生成障碍发挥抗阿尔兹海默病作用
- 批准号:2025JJ70209
- 批准年份:2025
- 资助金额:0.0 万元
- 项目类别:省市级项目
AGE-RAGE通路调控慢性胰腺炎纤维化进程的作用及分子机制
- 批准号:
- 批准年份:2024
- 资助金额:0 万元
- 项目类别:面上项目
甜茶抑制AGE-RAGE通路增强突触可塑性改善小鼠抑郁样行为
- 批准号:2023JJ50274
- 批准年份:2023
- 资助金额:0.0 万元
- 项目类别:省市级项目
蒙药额尔敦-乌日勒基础方调控AGE-RAGE信号通路改善术后认知功能障碍研究
- 批准号:
- 批准年份:2022
- 资助金额:33 万元
- 项目类别:地区科学基金项目
补肾健脾祛瘀方调控AGE/RAGE信号通路在再生障碍性贫血骨髓间充质干细胞功能受损的作用与机制研究
- 批准号:
- 批准年份:2022
- 资助金额:52 万元
- 项目类别:面上项目
LncRNA GAS5在2型糖尿病动脉粥样硬化中对AGE-RAGE 信号通路上相关基因的调控作用及机制研究
- 批准号:n/a
- 批准年份:2022
- 资助金额:10.0 万元
- 项目类别:省市级项目
围绕GLP1-Arginine-AGE/RAGE轴构建探针组学方法探索大柴胡汤异病同治的效应机制
- 批准号:81973577
- 批准年份:2019
- 资助金额:55.0 万元
- 项目类别:面上项目
AGE/RAGE通路microRNA编码基因多态性与2型糖尿病并发冠心病的关联研究
- 批准号:81602908
- 批准年份:2016
- 资助金额:18.0 万元
- 项目类别:青年科学基金项目
高血糖激活滑膜AGE-RAGE-PKC轴致骨关节炎易感的机制研究
- 批准号:81501928
- 批准年份:2015
- 资助金额:18.0 万元
- 项目类别:青年科学基金项目
相似海外基金
The Phenomenon of Stem Cell Aging according to Methylation Estimates of Age After Hematopoietic Stem Cell Transplantation
根据造血干细胞移植后甲基化年龄估算干细胞衰老现象
- 批准号:
23K07844 - 财政年份:2023
- 资助金额:
$ 32.69万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Analysis of Age-dependent Functional Changes in Skeletal Muscle CB1 Receptors by an in Vitro Model of Aging-related Muscle Atrophy
通过衰老相关性肌肉萎缩的体外模型分析骨骼肌 CB1 受体的年龄依赖性功能变化
- 批准号:
22KJ2960 - 财政年份:2023
- 资助金额:
$ 32.69万 - 项目类别:
Grant-in-Aid for JSPS Fellows
Joint U.S.-Japan Measures for Aging and Dementia Derived from the Prevention of Age-Related and Noise-induced Hearing Loss
美日针对预防与年龄相关和噪声引起的听力损失而导致的老龄化和痴呆症联合措施
- 批准号:
23KK0156 - 财政年份:2023
- 资助金额:
$ 32.69万 - 项目类别:
Fund for the Promotion of Joint International Research (International Collaborative Research)
The Effects of Muscle Fatigability on Gait Instability in Aging and Age-Related Falls Risk
肌肉疲劳对衰老步态不稳定性和年龄相关跌倒风险的影响
- 批准号:
10677409 - 财政年份:2023
- 资助金额:
$ 32.69万 - 项目类别:
Characterizing gut physiology by age, frailty, and sex: assessing the role of the aging gut in "inflamm-aging"
按年龄、虚弱和性别表征肠道生理学特征:评估衰老肠道在“炎症衰老”中的作用
- 批准号:
497927 - 财政年份:2023
- 资助金额:
$ 32.69万 - 项目类别:
Deciphering the role of osteopontin in the aging eye and age-related macular degeneration
破译骨桥蛋白在眼睛老化和年龄相关性黄斑变性中的作用
- 批准号:
10679287 - 财政年份:2023
- 资助金额:
$ 32.69万 - 项目类别:
Role of AGE/RAGEsignaling as a driver of pathological aging in the brain
AGE/RAGE信号传导作为大脑病理性衰老驱动因素的作用
- 批准号:
10836835 - 财政年份:2023
- 资助金额:
$ 32.69万 - 项目类别:
Elucidation of the protein kinase NLK-mediated aging mechanisms and treatment of age-related diseases
阐明蛋白激酶NLK介导的衰老机制及年龄相关疾病的治疗
- 批准号:
23K06378 - 财政年份:2023
- 资助金额:
$ 32.69万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Underlying mechanisms of age-related changes in ingestive behaviors: From the perspective of the aging brain and deterioration of the gustatory system.
与年龄相关的摄入行为变化的潜在机制:从大脑老化和味觉系统退化的角度来看。
- 批准号:
23K10845 - 财政年份:2023
- 资助金额:
$ 32.69万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Targeting Age-Activated Proinflammatory Chemokine Signaling by CCL2/11 to Enhance Skeletal Muscle Regeneration in Aging
通过 CCL2/11 靶向年龄激活的促炎趋化因子信号传导以增强衰老过程中的骨骼肌再生
- 批准号:
478877 - 财政年份:2023
- 资助金额:
$ 32.69万 - 项目类别:
Operating Grants