COMPLEMENT CONVERTASE: ASSEMBLY, FUNCTION AND REGULATION

补充转化酶:组装、功能和调节

基本信息

  • 批准号:
    8437634
  • 负责人:
  • 金额:
    $ 30.69万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2003
  • 资助国家:
    美国
  • 起止时间:
    2003-04-01 至 2017-08-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): The complement alternative activation pathway (AP) is a principal cause of tissue damage in human diseases and injury states. Therapeutic agents designed to inhibit harmful complement activity have begun to emerge in the clinical setting. The C3 convertases are the key enzymes of complement activation. Complement-related disease and injury can be traced both to inappropriate convertase assembly (e.g. autoimmunity), and to convertase regulator dysfunction (e.g. atypical HUS, age-related macular degeneration). The control of convertase assembly and regulation is the key to therapeutic strategies for prevention of complement-related damage. Our long-range goal is to design new approaches for the prevention or inhibition of harmful complement. Of the three complement activation pathways, the alternative pathway (AP) in particular has been implicated in numerous disease and injury states. This proposal is directed to the AP and specifically to properdin, a component unique to the AP convertases and whose functions are not yet fully understood. Recently we, and others, have employed animal model systems to demonstrate that properdin is a promising therapeutic target for the amelioration of AP-dependent pathogenesis. In order to understand the mechanistic basis of properdin function and to develop a properdin-based strategy for the therapeutic inhibition of AP- dependent complement activity, we propose the following SPECIFIC AIMS: Specific Aim 1. Use in vitro model systems to characterize the contribution of properdin pattern recognition activity to C activation. Specific Aim 2. Elucidate the role(s) of properdin in animal models of AP-dependent pathogenesis. Specific Aim 3. Develop anti-properdin reagents for the therapeutic inhibition of pathologic AP-dependent C activity. We expect the results from this work to have the potential to be highly translational and to significantly impact therapeutic strategies aimed at controlling the complement alternative pathway. PUBLIC HEALTH RELEVANCE: The complement proteins protect us from infectious microorganisms but under other circumstances they can cause severe and potentially life-threatening tissue damage. The proposed research will provide new strategies and tools for successful therapeutic intervention in such cases.
描述(由申请人提供):补体替代激活途径(AP)是人类疾病和损伤状态下组织损伤的主要原因。旨在抑制有害补体活性的治疗剂已经开始出现在临床环境中。C3转化酶是补体活化的关键酶。补体相关疾病和损伤可追溯至不适当的转换酶组装(如自身免疫)和转换酶调节功能障碍(如非典型溶血性尿毒综合征,年龄相关性黄斑变性)。控制转化酶的组装和调节是预防补体相关损伤的治疗策略的关键。我们的长期目标是设计预防或抑制有害补体的新方法。在三种补体激活途径中,替代途径(AP)尤其与许多疾病和损伤状态有关。这个建议是针对AP的,特别是针对properdin的,properdin是AP转换的唯一组件,其功能尚未完全理解。最近,我们和其他人使用动物模型系统来证明properdin是改善ap依赖性发病机制的有希望的治疗靶点。为了了解properdin功能的机制基础,并开发一种基于properdin的治疗性抑制AP依赖性补体活性的策略,我们提出以下具体目标:使用体外模型系统表征适当的模式识别活性对C激活的贡献。具体目标2。阐明properdin在ap依赖性发病机制动物模型中的作用。具体目标3。开发抗properdin试剂用于治疗性抑制病理性ap依赖性C活性。我们期望这项工作的结果具有高度翻译的潜力,并显著影响旨在控制补体替代途径的治疗策略。

项目成果

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DENNIS EMIL HOURCADE其他文献

DENNIS EMIL HOURCADE的其他文献

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{{ truncateString('DENNIS EMIL HOURCADE', 18)}}的其他基金

Cellular Models of a Monogenic Small Vessel Disease of the Brain
脑单基因小血管疾病的细胞模型
  • 批准号:
    10307638
  • 财政年份:
    2020
  • 资助金额:
    $ 30.69万
  • 项目类别:
Analysis of Complement Activation and Regulation by Mass Cytometry
通过质谱流式细胞术分析补体激活和调节
  • 批准号:
    9235239
  • 财政年份:
    2016
  • 资助金额:
    $ 30.69万
  • 项目类别:
Characterization/bioinformatics-modeling of nanoparticle:complement interactions
纳米粒子的表征/生物信息学建模:补体相互作用
  • 批准号:
    8323416
  • 财政年份:
    2010
  • 资助金额:
    $ 30.69万
  • 项目类别:
Characterization/bioinformatics-modeling of nanoparticle:complement interactions
纳米粒子的表征/生物信息学建模:补体相互作用
  • 批准号:
    8068114
  • 财政年份:
    2010
  • 资助金额:
    $ 30.69万
  • 项目类别:
Characterization/bioinformatics-modeling of nanoparticle:complement interactions
纳米粒子的表征/生物信息学建模:补体相互作用
  • 批准号:
    8150949
  • 财政年份:
    2010
  • 资助金额:
    $ 30.69万
  • 项目类别:
Complement Convertase: Assembly, Function and Regulation
补体转化酶:组装、功能和调节
  • 批准号:
    8070077
  • 财政年份:
    2010
  • 资助金额:
    $ 30.69万
  • 项目类别:
Complement Convertase: Assembly, Function and Regulation
补体转化酶:组装、功能和调节
  • 批准号:
    6616462
  • 财政年份:
    2003
  • 资助金额:
    $ 30.69万
  • 项目类别:
Complement Convertase: Assembly, Function and Regulation
补体转化酶:组装、功能和调节
  • 批准号:
    7800882
  • 财政年份:
    2003
  • 资助金额:
    $ 30.69万
  • 项目类别:
COMPLEMENT CONVERTASE: ASSEMBLY, FUNCTION AND REGULATION
补充转化酶:组装、功能和调节
  • 批准号:
    8897952
  • 财政年份:
    2003
  • 资助金额:
    $ 30.69万
  • 项目类别:
Complement Convertase: Assembly, Function and Regulation
补体转化酶:组装、功能和调节
  • 批准号:
    8055493
  • 财政年份:
    2003
  • 资助金额:
    $ 30.69万
  • 项目类别:

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