Role of GPNMB signaling in remyelination by oligodendrocyte progenitor cells

GPNMB 信号在少突胶质祖细胞髓鞘再生中的作用

基本信息

  • 批准号:
    10431034
  • 负责人:
  • 金额:
    $ 7.78万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-04-01 至 2024-03-31
  • 项目状态:
    已结题

项目摘要

ABSTRACT Loss of oligodendrocytes gives rise to demyelination, ultimately resulting in axonal degeneration and debilitating clinical outcomes in diseases like Multiple Sclerosis. While remyelination can prevent neurodegeneration, there are currently no approved therapies for promoting remyelination. Thus, there is an urgent need to identify factors that control remyelination. Oligodendrocyte progenitor cells (OPCs) in the adult brain are one of the key sources of remyelinating oligodendrocytes. However in chronic demyelination, they are inefficient for remyelination due to depletion and/or a block in their maturation. Using a combination of bioinformatic analysis and remyelination studies in mice, we discovered a novel mediator of the 7*)? pathway, Gpnmb which is highly expressed along with its receptor CD44 in response to demyelination. Gpnmb is a transmembrane protein that is cleaved by proteases into an intracellular domain (Gpnmb-ICD) and an ectodomain (Gpnmb-ECD). While Gpnmb-ICD can signal intrinsically by translocating to the nucleus, the released Gpnmb-ECD functions as an autocrine or paracrine signal by interacting with CD44 receptor in the same cell or a neighboring cell respectively. In the first aim, we will define the cell-autonomous function of Gpnmb in oligodendrocyte progenitor cells and in the second aim, we will determine the combined effect of intrinsic and extrinsic Gpnmb signaling on OPCs following cuprizone induced demyelination. Together, these studies will not only help elucidate the molecular mechanisms involved in maturation of adult OPCs but may also identify therapeutic targets for promoting remyelination.
摘要 少突胶质细胞的损失引起脱髓鞘,最终导致轴突变性和衰弱。 多发性硬化症等疾病的临床结果。虽然髓鞘再生可以防止神经变性, 目前还没有批准的促进髓鞘再生的疗法。因此,迫切需要查明各种因素, 控制髓鞘再生成人大脑中的少突胶质祖细胞(OPCs)是关键来源之一 髓鞘再生少突胶质细胞然而,在慢性脱髓鞘中,它们对髓鞘再生无效, 耗尽和/或阻断其成熟。结合生物信息学分析和髓鞘再生 在小鼠的研究中,我们发现了一种新的介体7*)?途径,Gpnmb,它是高表达的沿着 其受体CD 44对脱髓鞘的反应。GPNMB是一种跨膜蛋白, 在一个实施方案中,所述蛋白酶被编码为胞内结构域(Gpnmb-ICD)和胞外域(Gpnmb-ECD)。虽然Gpnmb-ICD可以 通过易位到细胞核内在地发出信号,释放的Gpnmb-ECD作为自分泌或 通过分别与同一细胞或相邻细胞中的CD 44受体相互作用来产生旁分泌信号。上 目的是,我们将确定Gpnmb在少突胶质细胞祖细胞中的细胞自主功能, 我们的目的是确定内源性和外源性Gpnmb信号转导对OPCs的联合作用, 铜腙诱导的脱髓鞘。总之,这些研究不仅有助于阐明 参与成年OPCs的成熟,但也可能确定促进髓鞘再生的治疗靶点。

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 }}

Jayshree Samanta其他文献

Jayshree Samanta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('Jayshree Samanta', 18)}}的其他基金

Novel Modulators of TGFß1 signaling in regulation of remyelination by neural stem cells
TGFα1 信号传导在神经干细胞髓鞘再生调节中的新型调节剂
  • 批准号:
    10544041
  • 财政年份:
    2022
  • 资助金额:
    $ 7.78万
  • 项目类别:
Novel Modulators of TGFß1 signaling in regulation of remyelination by neural stem cells
TGFα1 信号传导在神经干细胞髓鞘再生调节中的新型调节剂
  • 批准号:
    10366677
  • 财政年份:
    2022
  • 资助金额:
    $ 7.78万
  • 项目类别:
Role of GPNMB Signaling in Remyelination by Oligodendrocyte Progenitor Cells
GPNMB 信号在少突胶质祖细胞髓鞘再生中的作用
  • 批准号:
    10596170
  • 财政年份:
    2022
  • 资助金额:
    $ 7.78万
  • 项目类别:

相似海外基金

Co-designing a lifestyle, stop-vaping intervention for ex-smoking, adult vapers (CLOVER study)
为戒烟的成年电子烟使用者共同设计生活方式、戒烟干预措施(CLOVER 研究)
  • 批准号:
    MR/Z503605/1
  • 财政年份:
    2024
  • 资助金额:
    $ 7.78万
  • 项目类别:
    Research Grant
Early Life Antecedents Predicting Adult Daily Affective Reactivity to Stress
早期生活经历预测成人对压力的日常情感反应
  • 批准号:
    2336167
  • 财政年份:
    2024
  • 资助金额:
    $ 7.78万
  • 项目类别:
    Standard Grant
RAPID: Affective Mechanisms of Adjustment in Diverse Emerging Adult Student Communities Before, During, and Beyond the COVID-19 Pandemic
RAPID:COVID-19 大流行之前、期间和之后不同新兴成人学生社区的情感调整机制
  • 批准号:
    2402691
  • 财政年份:
    2024
  • 资助金额:
    $ 7.78万
  • 项目类别:
    Standard Grant
Migrant Youth and the Sociolegal Construction of Child and Adult Categories
流动青年与儿童和成人类别的社会法律建构
  • 批准号:
    2341428
  • 财政年份:
    2024
  • 资助金额:
    $ 7.78万
  • 项目类别:
    Standard Grant
Elucidation of Adult Newt Cells Regulating the ZRS enhancer during Limb Regeneration
阐明成体蝾螈细胞在肢体再生过程中调节 ZRS 增强子
  • 批准号:
    24K12150
  • 财政年份:
    2024
  • 资助金额:
    $ 7.78万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Understanding how platelets mediate new neuron formation in the adult brain
了解血小板如何介导成人大脑中新神经元的形成
  • 批准号:
    DE240100561
  • 财政年份:
    2024
  • 资助金额:
    $ 7.78万
  • 项目类别:
    Discovery Early Career Researcher Award
RUI: Evaluation of Neurotrophic-Like properties of Spaetzle-Toll Signaling in the Developing and Adult Cricket CNS
RUI:评估发育中和成年蟋蟀中枢神经系统中 Spaetzle-Toll 信号传导的神经营养样特性
  • 批准号:
    2230829
  • 财政年份:
    2023
  • 资助金额:
    $ 7.78万
  • 项目类别:
    Standard Grant
Usefulness of a question prompt sheet for onco-fertility in adolescent and young adult patients under 25 years old.
问题提示表对于 25 岁以下青少年和年轻成年患者的肿瘤生育力的有用性。
  • 批准号:
    23K09542
  • 财政年份:
    2023
  • 资助金额:
    $ 7.78万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Identification of new specific molecules associated with right ventricular dysfunction in adult patients with congenital heart disease
鉴定与成年先天性心脏病患者右心室功能障碍相关的新特异性分子
  • 批准号:
    23K07552
  • 财政年份:
    2023
  • 资助金额:
    $ 7.78万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Issue identifications and model developments in transitional care for patients with adult congenital heart disease.
成人先天性心脏病患者过渡护理的问题识别和模型开发。
  • 批准号:
    23K07559
  • 财政年份:
    2023
  • 资助金额:
    $ 7.78万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了