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Dual Targeting Mitochondria and GPCR in Retinal Protection

Dual Targeting Mitochondria and GPCR in Retinal Protection
双靶向线粒体和 GPCR 在视网膜保护中的作用
批准号:
10383538
负责人:
John D Ash
金额:
$25.57万
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
项目状态:
已结题
起止时间:
2022-09-01 至 2023-08-31

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中文摘要
翻译
项目摘要 治疗使光感受器和视网膜色素上皮(RPE)细胞恶化的视网膜变性 至今仍然有限。视网膜保护治疗设计的一个重大挑战是 退化机制单一目标干预措施无法有效减缓或改变 由于疾病相关途径的代偿机制导致的退行性过程。多目标干预是 对于包括神经变性在内复杂疾病的有效治疗越来越重要。然而,在这方面, 具有可干预视网膜变性中一种以上疾病相关途径的生物活性的化合物 还没有被探索。在这项提案中,我们将进行多靶点药物(CM-1)的体内治疗试验。 20)在视网膜保护中,通过双重靶向线粒体和G蛋白偶联受体(GPCR), 线粒体功能和生物发生以及减轻视网膜氧化损伤。两种视网膜病变小鼠模型 退化将被使用。一种是环境压力引起的视网膜变性,另一种是 遗传性视网膜疾病的遗传模型。我们将评估CM-20保护外层视网膜的功效, 线粒体和减少视网膜氧化应激。积极的结果将证明有效性临床试验, 人类视网膜变性并提供作用机制的机械知识。
英文摘要
PROJECT SUMMARY Treatment for retinal degeneration that deteriorates photoreceptors and retinal pigment epithelium (RPE) cells remains limited to date. A significant challenge for therapeutic design in retinal protection is the complexity of degenerative mechanism. Single target intervention would not be effective to slow down or modify the degenerative course due to compensatory mechanisms of disease-related pathways. Multi-target intervention is increasingly important for effective treatment of complex disease including neurodegeneration. However, compounds with bioactivity that can intervene more than one disease-related pathways in retinal degeneration have not been explored. In this proposal, we will conduct in vivo therapeutic testing of a multi-target drug (CM- 20) in retinal protection via dual targeting both mitochondria and a G-protein coupled receptor (GPCR) to improve mitochondrial function and biogenesis and to mitigate retinal oxidative damage. Two mouse models of retinal degeneration will be used. One is an environmental stressor-induced retinal degeneration, and the other one is a genetic model of inherited retinal disease. We will evaluate efficacy of CM-20 in protecting outer retina and mitochondria and in reducing retinal oxidative stress. Positive outcomes would justify efficacy clinical trial in human retinal degeneration and provide mechanistic knowledge in mechanism of action.
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Retinal Degeneration Conference
Transcriptional control of stress-induced resistance to retinal degeneration
  • 批准号:
    10477262
  • 项目类别:
  • 资助金额:
    $37.22万
  • 财政年份:
    2021
  • 负责人:
    John D Ash
  • 依托单位:
Transcriptional control of stress-induced resistance to retinal degeneration
  • 批准号:
    10296291
  • 项目类别:
  • 资助金额:
    $38.37万
  • 财政年份:
    2021
  • 负责人:
    John D Ash
  • 依托单位:
Transcriptional control of stress-induced resistance to retinal degeneration
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