Mechanisms of synaptic loss by the classical complement pathway in motor circuit development and disease

运动回路发育和疾病中经典补体途径突触损失的机制

基本信息

  • 批准号:
    10207406
  • 负责人:
  • 金额:
    $ 62.24万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2018
  • 资助国家:
    美国
  • 起止时间:
    2018-09-15 至 2023-06-30
  • 项目状态:
    已结题

项目摘要

Project Summary Motor circuits control fundamental behaviors such as swallowing, breathing and locomotion. Spinal motor neurons are the key mediators translating motor commands generated within the central nervous system to peripheral muscle targets. Motor neurons are activated by a precisely regulated pattern of synaptic activity from sensory neurons, local spinal interneurons and descending pathways from the brain. During early development, synaptic activity received by motor neurons shapes their functional properties. In contrast, gene mutations that induce perturbations in either neuronal wiring or synaptic drive received by motor neurons often result in motor system disorders. A prominent example of this situation is spinal muscular atrophy (SMA)—an inherited neuromuscular disease caused by ubiquitous deficiency in the survival motor neuron (SMN) protein. SMA pathogenesis involves alterations of multiple components of the motor circuit leading to abnormalities in spinal reflexes, motor neuron loss and skeletal muscle atrophy. However, the molecular, cellular and circuit mechanisms underlying SMA remain largely elusive. Our previous work have led us in uncovering synaptic dysfunction of proprioceptive origin as a key determinant event early in the disease process. Impaired function and eventual loss of the sensory-motor excitatory synapses induce changes in the expression of channels on the motor neuron membrane, resulting in reduced motor output. Unraveling therefore the molecular mechanisms responsible for synaptic dysfunction and loss would provide key insights into the disease mechanisms. In Aim 1, we will study whether complement proteins are responsible for the dysfunction and ultimately the elimination of vulnerable synapses in in SMA mice. To address this, we will employ mouse genetics together with morphological and functional assays. In Aim 2, we will investigate the role of certain key classical complement proteins in the assembly and refinement of sensory-motor circuits during normal development. We will also use mouse genetics, combined with morphological and functional assays to complete this part of the project. In Aim 3, we will probe into the molecular mechanisms that may cause the selective attack by aberrant activation of the immune system towards synapses under ubiquitous SMN deficiency in mouse models of the disease.
项目总结

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 }}

George Z Mentis其他文献

George Z Mentis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('George Z Mentis', 18)}}的其他基金

Cellular and neuronal circuit mechanisms involved in locomotor activity
参与运动活动的细胞和神经元回路机制
  • 批准号:
    10587675
  • 财政年份:
    2022
  • 资助金额:
    $ 62.24万
  • 项目类别:
Mechanisms of synaptic loss by the classical complement pathway in motor circuit development and disease
运动回路发育和疾病中经典补体途径突触损失的机制
  • 批准号:
    10442652
  • 财政年份:
    2018
  • 资助金额:
    $ 62.24万
  • 项目类别:
Mechanisms of synaptic loss by the classical complement pathway in motor circuit development and disease
运动回路发育和疾病中经典补体途径突触损失的机制
  • 批准号:
    10517958
  • 财政年份:
    2018
  • 资助金额:
    $ 62.24万
  • 项目类别:
Mechanisms of synaptic loss by the classical complement pathway in motor circuit development and disease
运动回路发育和疾病中经典补体途径突触损失的机制
  • 批准号:
    10661380
  • 财政年份:
    2018
  • 资助金额:
    $ 62.24万
  • 项目类别:
Generation of mice to selectively mark a subset of spinal interneurons
产生选择性标记脊髓中间神经元子集的小鼠
  • 批准号:
    9374839
  • 财政年份:
    2017
  • 资助金额:
    $ 62.24万
  • 项目类别:
Genetic evaluation of the p53 cell death pathway in spinal muscular atrophy (SMA)
脊髓性肌萎缩症 (SMA) 中 p53 细胞死亡途径的遗传评估
  • 批准号:
    8702765
  • 财政年份:
    2014
  • 资助金额:
    $ 62.24万
  • 项目类别:
A novel spinal circuit involved in locomotion
一种参与运动的新型脊髓回路
  • 批准号:
    8511482
  • 财政年份:
    2013
  • 资助金额:
    $ 62.24万
  • 项目类别:
A novel spinal circuit involved in locomotion
一种参与运动的新型脊髓回路
  • 批准号:
    8616414
  • 财政年份:
    2013
  • 资助金额:
    $ 62.24万
  • 项目类别:
Mechanisms of Central Synaptic Dysfunction in SMA
SMA 中枢突触功能障碍的机制
  • 批准号:
    8822939
  • 财政年份:
    2012
  • 资助金额:
    $ 62.24万
  • 项目类别:
Mechanisms of Central Synaptic Dysfunction in SMA
SMA 中枢突触功能障碍的机制
  • 批准号:
    9448504
  • 财政年份:
    2012
  • 资助金额:
    $ 62.24万
  • 项目类别:

相似海外基金

RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
  • 批准号:
    2327346
  • 财政年份:
    2024
  • 资助金额:
    $ 62.24万
  • 项目类别:
    Standard Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
  • 批准号:
    2312555
  • 财政年份:
    2024
  • 资助金额:
    $ 62.24万
  • 项目类别:
    Standard Grant
How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
  • 批准号:
    BB/Z514391/1
  • 财政年份:
    2024
  • 资助金额:
    $ 62.24万
  • 项目类别:
    Training Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
  • 批准号:
    ES/Z502595/1
  • 财政年份:
    2024
  • 资助金额:
    $ 62.24万
  • 项目类别:
    Fellowship
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
  • 批准号:
    ES/Z000149/1
  • 财政年份:
    2024
  • 资助金额:
    $ 62.24万
  • 项目类别:
    Research Grant
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
  • 批准号:
    23K24936
  • 财政年份:
    2024
  • 资助金额:
    $ 62.24万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
  • 批准号:
    2901648
  • 财政年份:
    2024
  • 资助金额:
    $ 62.24万
  • 项目类别:
    Studentship
ERI: Developing a Trust-supporting Design Framework with Affect for Human-AI Collaboration
ERI:开发一个支持信任的设计框架,影响人类与人工智能的协作
  • 批准号:
    2301846
  • 财政年份:
    2023
  • 资助金额:
    $ 62.24万
  • 项目类别:
    Standard Grant
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
  • 批准号:
    488039
  • 财政年份:
    2023
  • 资助金额:
    $ 62.24万
  • 项目类别:
    Operating Grants
How motor impairments due to neurodegenerative diseases affect masticatory movements
神经退行性疾病引起的运动障碍如何影响咀嚼运动
  • 批准号:
    23K16076
  • 财政年份:
    2023
  • 资助金额:
    $ 62.24万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了