Investigating how intestinal innate immunity confers neuroprotection using C. elegans

使用线虫研究肠道先天免疫如何赋予神经保护作用

基本信息

  • 批准号:
    9576370
  • 负责人:
  • 金额:
    $ 32.83万
  • 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:
    2018-08-15 至 2023-04-30
  • 项目状态:
    已结题

项目摘要

1 Mitochondrial homeostasis is required to maintain neuronal health and function, and its 2 dysregulation plays prominent roles in rendering specific neural systems vulnerable. Recently 3 we have found that the activation of the p38 mitogen-activated protein kinase (MAPK; the 4 mammalian p38α ortholog) and the CREB like transcription factor ATF-7-mediated innate 5 immune pathway in the intestine of C. elegans can protect its neurons from degeneration 6 induced by mitochondrial dysfunction. The neuroprotective effects of p38MAPK/ATF-7 7 immunity activated in the gut occurs through the enhancement of mitophagy, and 8 p38MAPK/ATF-7 activity in intestinal cells alone is sufficient to lower mitochondrial numbers, 9 not only in intestinal cells, but also in neurons. Moreover, preliminary data obtained in our lab 10 show that in C. elegans the peripheral increase in disease-related misfolded proteins can 11 disrupt innate immune signaling pathways. Our central hypothesis, therefore, is that 12 aging- and proteotoxicity-induced dysregulation of the immune system can disrupt 13 mitochondrial homeostasis in neurons initiating or aggravating neurodegeneration. 14 The objective of the proposed research is to determine how the p38MAPK/ATF-7-mediated 15 innate immune pathway activated in the gut in C. elegans affects mitochondrial homeostasis 16 in neurons. To do this, we will: 17 18 Aim 1: Examine the role of the innate immune response in the maintenance of neurons 19 upon Complex I dysfunction. 20 Aim 2: Identify the immune mediators in the gut that affect neuronal health. 21 Aim 3: Examine the role of peripheral proteotoxic antigens in disrupting immune signaling, 22 leading to the accumulation of dysfunctional neuronal mitochondria. 23 24 Our preliminary data show that the innate immune response modulates mitochondrial 25 homeostasis in a cell non-autonomous manner, and is in turn can be inhibited by specific 26 peripheral proteotoxic antigens. These studies therefore offer the novel possibility that 27 immunosenescence is responsible for the accumulation of dysfunctional mitochondria, and 28 could offer new insights into the role of proteotoxicity in the modulation of mitochondrial 29 homeostasis.
线粒体内稳态是维持神经元健康和功能的必要条件

项目成果

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Veena Prahlad其他文献

Veena Prahlad的其他文献

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{{ truncateString('Veena Prahlad', 18)}}的其他基金

Investigating how stress induced changes in maternal serotonin affect offspring development and stress resilience
研究压力引起的母亲血清素变化如何影响后代发育和压力恢复能力
  • 批准号:
    10893245
  • 财政年份:
    2022
  • 资助金额:
    $ 32.83万
  • 项目类别:
Investigating how stress induced changes in maternal serotonin affect offspring development and stress resilience
研究压力引起的母亲血清素变化如何影响后代发育和压力恢复能力
  • 批准号:
    10602537
  • 财政年份:
    2022
  • 资助金额:
    $ 32.83万
  • 项目类别:
Investigating how stress induced changes in maternal serotonin affect offspring development and stress resilience
研究压力引起的母亲血清素变化如何影响后代发育和压力恢复能力
  • 批准号:
    10444181
  • 财政年份:
    2022
  • 资助金额:
    $ 32.83万
  • 项目类别:
Metabolism, Aging, Pathogenesis, Stress and Small RNAs Meeting
新陈代谢、衰老、发病机制、压力和小 RNA 会议
  • 批准号:
    9990946
  • 财政年份:
    2021
  • 资助金额:
    $ 32.83万
  • 项目类别:
Investigating how intestinal innate immunity confers neuroprotection using C. elegans
使用线虫研究肠道先天免疫如何赋予神经保护作用
  • 批准号:
    9926205
  • 财政年份:
    2018
  • 资助金额:
    $ 32.83万
  • 项目类别:
Investigating how intestinal innate immunity confers neuroprotection using C. elegans
使用线虫研究肠道先天免疫如何赋予神经保护作用
  • 批准号:
    9764236
  • 财政年份:
    2018
  • 资助金额:
    $ 32.83万
  • 项目类别:
Investigating how intestinal innate immunity confers neuroprotection using C. elegans
使用线虫研究肠道先天免疫如何赋予神经保护作用
  • 批准号:
    10186678
  • 财政年份:
    2018
  • 资助金额:
    $ 32.83万
  • 项目类别:
Investigating how intestinal innate immunity confers neuroprotection using C. elegans
使用线虫研究肠道先天免疫如何赋予神经保护作用
  • 批准号:
    10425212
  • 财政年份:
    2018
  • 资助金额:
    $ 32.83万
  • 项目类别:
Uncovering how serotonergic signaling non-autonomously regulates protein homeostasis
揭示血清素信号如何非自主调节蛋白质稳态
  • 批准号:
    9904301
  • 财政年份:
    2016
  • 资助金额:
    $ 32.83万
  • 项目类别:
Uncovering how serotonergic signaling non-autonomously regulates protein homeostasis
揭示血清素信号如何非自主调节蛋白质稳态
  • 批准号:
    9103670
  • 财政年份:
    2016
  • 资助金额:
    $ 32.83万
  • 项目类别:

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活体动物的 Pexophagy 调节及其在衰老和长寿中的作用
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