Inflammasome-based Alzheimer's disease therapy in the context of diabetes

糖尿病背景下基于炎症小体的阿尔茨海默病治疗

基本信息

  • 批准号:
    10287353
  • 负责人:
  • 金额:
    $ 40.37万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-09-01 至 2025-05-31
  • 项目状态:
    未结题

项目摘要

Scope of Work / Abstract This Administrative Supplement proposal is to investigate the role of inflammasome signaling in models of Alzheimer's disease (AD) complicated by diabetes mellitus (DM). AD is a progressive neurodegeneration accounting for 60-70% of all the dementia worldwide. DM, the metabolic syndrome responsible for a variety of complications including diabetic retinopathy (the subject of the parent proposal), is characterized by hyperglycemia, hyperinsulinemia, and insulin resistance. Numerous epidemiologic analyses have identified DM as a significant risk factor and comorbidity for AD. In addition, DM and AD share inflammasome activation as pathomechanisms, and each entity has independently been shown to be responsive to inflammasome inhibition. We propose to test the overall hypothesis that inflammasome inhibition reduces neuroinflammation and improves cognitive outcomes in mouse AD models that are complicated by the co-morbidity of DM. To accomplish this, we will critically assess the spatial and temporal kinetics of inflammasome activation in the brain in combined DM/AD models. In addition, we will test whether the presence of DM affects the efficacy of inflammasome inhibition on cognitive outcomes of AD mouse models. As such, this supplement request focused on AD is within the scope of the active parent NIH award and has the potential to stimulate new studies for examining novel molecular and biochemical mechanisms of inflammasome activation in AD in the presence of metabolic disorders. We predict that establishing inflammasome as a key link between DM and AD will stimulate additional activity on the part of endocrinologists, immunologists, and neurobiologists thereby leading to progress in deciphering and potentially treating AD and related dementias complicated by DM. This supplement will also enable our laboratory to develop a focus on AD and related dementias by generating additional experimental data that can be leveraged to submit new proposals focused directly on AD and related dementias.
工作范围/摘要 这项行政补充建议是为了调查炎性小体信号在 阿尔茨海默病(AD)合并糖尿病(DM)模型。广告是进步的 神经变性占全球痴呆症总数的60%-70%。DM,新陈代谢 导致各种并发症的综合征,包括糖尿病视网膜病变(主题为 父建议),以高血糖、高胰岛素血症和胰岛素抵抗为特征。 许多流行病学分析已确认糖尿病是一个重要的危险因素和共病 对于AD。此外,糖尿病和阿尔茨海默病的共同病理机制是炎性小体激活,并且各自 实体已被证明对炎性小体抑制有反应。我们建议 为了检验炎性小体抑制减少神经炎症和 改善因共同发病而复杂的小鼠AD模型的认知结果 DM。为了实现这一点,我们将批判性地评估 DM/AD联合模型中脑内炎性小体激活。此外,我们还将测试是否 糖尿病的存在影响炎症抑制对阿尔茨海默病认知结局的影响 老鼠模型。因此,此针对AD的补充请求属于Active 母公司NIH奖,并有可能刺激新的研究,以检查新的分子 代谢异常时AD炎性小体激活的生化机制 精神错乱。我们预测,建立炎症体是DM和AD之间的关键环节 将刺激内分泌学家、免疫学家和 神经生物学家因此在破译和潜在治疗AD及相关疾病方面取得了进展 糖尿病并发痴呆。这一补充也将使我们的实验室能够制定一个重点 通过生成可利用的附加实验数据来解决AD和相关痴呆问题 提交直接针对AD和相关痴呆症的新提案。

项目成果

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Jayakrishna Ambati其他文献

Jayakrishna Ambati的其他文献

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{{ truncateString('Jayakrishna Ambati', 18)}}的其他基金

Cytosolic SINE retrotransposable element cDNA and mitochondrial DNA in aging retina
衰老视网膜中的胞质 SINE 逆转录转座元件 cDNA 和线粒体 DNA
  • 批准号:
    10722062
  • 财政年份:
    2023
  • 资助金额:
    $ 40.37万
  • 项目类别:
Defining the role of SINE retrotransposons and inflammasome activation in Alzheimer's disease
定义 SINE 逆转录转座子和炎症小体激活在阿尔茨海默病中的作用
  • 批准号:
    10696066
  • 财政年份:
    2022
  • 资助金额:
    $ 40.37万
  • 项目类别:
Defining the role of SINE retrotransposons and inflammasome activation in Alzheimer's disease
定义 SINE 逆转录转座子和炎症小体激活在阿尔茨海默病中的作用
  • 批准号:
    10517678
  • 财政年份:
    2022
  • 资助金额:
    $ 40.37万
  • 项目类别:
Nlrp3 inflammasome activation in early diabetic retinopathy - Administrative Supplement ERG Request
早期糖尿病视网膜病变中 Nlrp3 炎症小体激活 - 行政补充 ERG 请求
  • 批准号:
    10643583
  • 财政年份:
    2020
  • 资助金额:
    $ 40.37万
  • 项目类别:
Nlrp3 inflammasome activation in early diabetic retinopathy
早期糖尿病视网膜病变中 Nlrp3 炎性体激活
  • 批准号:
    10414049
  • 财政年份:
    2020
  • 资助金额:
    $ 40.37万
  • 项目类别:
Nlrp3 inflammasome activation in early diabetic retinopathy
早期糖尿病视网膜病变中 Nlrp3 炎性体激活
  • 批准号:
    10626060
  • 财政年份:
    2020
  • 资助金额:
    $ 40.37万
  • 项目类别:
Visual system and cognitive biology in normal animals versus in an animal model of Alzheimer's disease with or without diabetes treated with solo or dual inflammasome inhibitors
正常动物的视觉系统和认知生物学与单独或双重炎性体抑制剂治疗的患有或不患有糖尿病的阿尔茨海默病动物模型的比较
  • 批准号:
    10712956
  • 财政年份:
    2020
  • 资助金额:
    $ 40.37万
  • 项目类别:
Non-canonical inflammasome in activation in RPE degeneration
RPE 变性中激活的非典型炎症小体
  • 批准号:
    10338080
  • 财政年份:
    2019
  • 资助金额:
    $ 40.37万
  • 项目类别:
Antigen-independent suppression of ocular angiogenesis via the Fc receptor
通过 Fc 受体对眼部血管生成进行抗原非依赖性抑制
  • 批准号:
    10003425
  • 财政年份:
    2018
  • 资助金额:
    $ 40.37万
  • 项目类别:
Antigen-independent suppression of ocular angiogenesis via the Fc receptor
通过 Fc 受体对眼部血管生成进行抗原非依赖性抑制
  • 批准号:
    9765313
  • 财政年份:
    2018
  • 资助金额:
    $ 40.37万
  • 项目类别:

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