Mechanisms of age-related susceptibility of NMJ function

NMJ 功能与年龄相关的易感性机制

基本信息

  • 批准号:
    10161705
  • 负责人:
  • 金额:
    $ 40.68万
  • 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:
    2017-07-01 至 2023-05-31
  • 项目状态:
    已结题

项目摘要

ABSTRACT The goal of this application is to determine the role of trophic interactions in the susceptibility (or resilience) to the effects of aging on the neuromuscular system. Age-related neuromuscular dysfunction is an important determinant of overall health, limiting independence, increasing frailty and predisposing individuals to age- related co-morbidities and mortality. Interactions between motoneurons and the muscle fibers they innervate determine muscle fiber properties and have a significant impact on muscle function throughout the lifespan. Motoneuron-muscle fiber interactions are likely exerted via trophic factors that vary across muscle groups. Brain-derived neurotrophic factor (BDNF) acting via its high-affinity receptor tropomyosin related kinase receptor (TrkB) has a known role in the maintenance of the adult NMJ. However, the role of BDNF/TrkB signaling in old age is not presently understood. Exciting recent studies show that inhibition of TrkB kinase activity exerts deleterious effects on neuromuscular transmission that vary across age groups, replicating the effects of old age at young NMJs. The current proposal will use a combination of highly-innovative methods to explore mechanistically the role of disrupted trophic factor signaling at the NMJ in old age. Our working hypothesis is that susceptibility to age-related neuromuscular dysfunction depends on motoneuron-muscle fiber trophic influences exerted by BDNF/TrkB signaling at the NMJ (aim 1) and motoneuron (aim 2). Furthermore, trophic factors can determine susceptibility to neuromuscular damage resulting from autophagy imbalance causing accumulation of protein aggregates and degeneration in old age. Two specific aims are proposed: Specific Aim 1) To determine the cellular (trophic factor dependent) mechanisms underlying susceptibility to neuromuscular dysfunction in old age. Specific Aim 2) To determine the molecular (trophic factor dependent) mechanisms underlying age-related effects at motoneurons. These results constitute the necessary foundation for the development of targeted therapies to mitigate aging effects on neuromuscular performance and increase the health span in the aging population with therapies initiated later in life to combat frailty and disability.
摘要

项目成果

期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Uptake and intracellular fate of cholera toxin subunit b-modified mesoporous silica nanoparticle-supported lipid bilayers (aka protocells) in motoneurons.
{{ 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 }}

Carlos B Mantilla其他文献

Carlos B Mantilla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('Carlos B Mantilla', 18)}}的其他基金

Prediction and early recognition of opioid-induced respiratory depression
阿片类药物引起的呼吸抑制的预测和早期识别
  • 批准号:
    10426828
  • 财政年份:
    2022
  • 资助金额:
    $ 40.68万
  • 项目类别:
Prediction and early recognition of opioid-induced respiratory depression
阿片类药物引起的呼吸抑制的预测和早期识别
  • 批准号:
    10593973
  • 财政年份:
    2022
  • 资助金额:
    $ 40.68万
  • 项目类别:
Enhancing Respiratory Motor Function after Spinal Cord Injury
增强脊髓损伤后的呼吸运动功能
  • 批准号:
    10675888
  • 财政年份:
    2019
  • 资助金额:
    $ 40.68万
  • 项目类别:
Enhancing Respiratory Motor Function after Spinal Cord Injury
增强脊髓损伤后的呼吸运动功能
  • 批准号:
    10083760
  • 财政年份:
    2019
  • 资助金额:
    $ 40.68万
  • 项目类别:
Enhancing Respiratory Motor Function after Spinal Cord Injury
增强脊髓损伤后的呼吸运动功能
  • 批准号:
    10323658
  • 财政年份:
    2019
  • 资助金额:
    $ 40.68万
  • 项目类别:
Mechanisms of age-related susceptibility of NMJ function
NMJ 功能与年龄相关的易感性机制
  • 批准号:
    9921270
  • 财政年份:
    2017
  • 资助金额:
    $ 40.68万
  • 项目类别:
Respiratory Control in Old Age
老年呼吸控制
  • 批准号:
    8871511
  • 财政年份:
    2013
  • 资助金额:
    $ 40.68万
  • 项目类别:
Respiratory Control in Old Age
老年呼吸控制
  • 批准号:
    10740986
  • 财政年份:
    2013
  • 资助金额:
    $ 40.68万
  • 项目类别:
Respiratory Control in Old Age
老年呼吸控制
  • 批准号:
    9895586
  • 财政年份:
    2013
  • 资助金额:
    $ 40.68万
  • 项目类别:
Respiratory Control in Old Age
老年呼吸控制
  • 批准号:
    8665855
  • 财政年份:
    2013
  • 资助金额:
    $ 40.68万
  • 项目类别:

相似海外基金

Construction of affinity sensors using high-speed oscillation of nanomaterials
利用纳米材料高速振荡构建亲和传感器
  • 批准号:
    23H01982
  • 财政年份:
    2023
  • 资助金额:
    $ 40.68万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Affinity evaluation for development of polymer nanocomposites with high thermal conductivity and interfacial molecular design
高导热率聚合物纳米复合材料开发和界面分子设计的亲和力评估
  • 批准号:
    23KJ0116
  • 财政年份:
    2023
  • 资助金额:
    $ 40.68万
  • 项目类别:
    Grant-in-Aid for JSPS Fellows
Platform for the High Throughput Generation and Validation of Affinity Reagents
用于高通量生成和亲和试剂验证的平台
  • 批准号:
    10598276
  • 财政年份:
    2023
  • 资助金额:
    $ 40.68万
  • 项目类别:
Development of High-Affinity and Selective Ligands as a Pharmacological Tool for the Dopamine D4 Receptor (D4R) Subtype Variants
开发高亲和力和选择性配体作为多巴胺 D4 受体 (D4R) 亚型变体的药理学工具
  • 批准号:
    10682794
  • 财政年份:
    2023
  • 资助金额:
    $ 40.68万
  • 项目类别:
Collaborative Research: DESIGN: Co-creation of affinity groups to facilitate diverse & inclusive ornithological societies
合作研究:设计:共同创建亲和团体以促进多元化
  • 批准号:
    2233343
  • 财政年份:
    2023
  • 资助金额:
    $ 40.68万
  • 项目类别:
    Standard Grant
Collaborative Research: DESIGN: Co-creation of affinity groups to facilitate diverse & inclusive ornithological societies
合作研究:设计:共同创建亲和团体以促进多元化
  • 批准号:
    2233342
  • 财政年份:
    2023
  • 资助金额:
    $ 40.68万
  • 项目类别:
    Standard Grant
Molecular mechanisms underlying high-affinity and isotype switched antibody responses
高亲和力和同种型转换抗体反应的分子机制
  • 批准号:
    479363
  • 财政年份:
    2023
  • 资助金额:
    $ 40.68万
  • 项目类别:
    Operating Grants
Deconstructed T cell antigen recognition: Separation of affinity from bond lifetime
解构 T 细胞抗原识别:亲和力与键寿命的分离
  • 批准号:
    10681989
  • 财政年份:
    2023
  • 资助金额:
    $ 40.68万
  • 项目类别:
CAREER: Engineered Affinity-Based Biomaterials for Harnessing the Stem Cell Secretome
职业:基于亲和力的工程生物材料用于利用干细胞分泌组
  • 批准号:
    2237240
  • 财政年份:
    2023
  • 资助金额:
    $ 40.68万
  • 项目类别:
    Continuing Grant
ADVANCE Partnership: Leveraging Intersectionality and Engineering Affinity groups in Industrial Engineering and Operations Research (LINEAGE)
ADVANCE 合作伙伴关系:利用工业工程和运筹学 (LINEAGE) 领域的交叉性和工程亲和力团体
  • 批准号:
    2305592
  • 财政年份:
    2023
  • 资助金额:
    $ 40.68万
  • 项目类别:
    Continuing Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了