Green tea derived EGCG opposes AIDS dementia-like neuronal damage

绿茶提取的 EGCG 可以对抗艾滋病痴呆样神经元损伤

基本信息

  • 批准号:
    7460708
  • 负责人:
  • 金额:
    $ 18.38万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2007
  • 资助国家:
    美国
  • 起止时间:
    2007-07-05 至 2011-06-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Our long term goal is to develop effective agents for AIDS dementia complex. The purpose of this project is to investigate if green tea EGCG, a known inhibitor of signal transducer and activation of transcription 1 (STAT1), could attenuate AIDS-like neuronal damage through disruption STAT1 signaling in mice exposed to IFN-g with HIV-1 proteins gp120 and Tat. A state of immune activation characterized by increased levels of pro-inflammatory cytokines is widely regarded as an important factor leading to AIDS dementia-like neuronal damage and a key regulator for pro-inflammatory signaling in neurons is STAT1. STAT1 activation is involved in neuronal injury/death associated with brain ischemia, as well as AIDS dementia. Moreover its "activator" IFN-g, has been shown to be elevated both in the cerebrospinal fluid and brains of HIV positive individuals. Results from our pilot studies suggest that IFN-g enhances the neurotoxic effects of gp120 and Tat. Further, AIDS dementia-like neuronal damage from this combined insult was largely attenuated in STAT1 deficient neurons. We and others have shown that the treatment of primary neurons with EGCG reduces STAT1 activation and resultant neuronal injury in models of AIDS dementia and stroke, respectively. We hypothesize that EGCG treatment will decrease AIDS dementia-like neuronal damage via STAT1 suppression. Aim 1 is to establish a mouse model representative of the possible neuronal damage exhibited in AIDS dementia. Aim 2 will characterize the role of STAT1 in mediating neuronal injury induced by IFN-g and gp120 and Tat in mice. To this end we will compare the neuronal damage in STAT1 deficient mice to control mice after intracerebroventricular injection of IFN-g with gp120 or Tat. We expect STAT1 deficient mice will show a marked decrease in AIDS dementia-like neuronal damage compared to control. Aim 3 will investigate the effects of EGCG on inhibition of the neuronal damage resulting from IFN-g mediated STAT1 activation in the presence of gp120 or Tat in mice. Here we also plan to delineate the most effective EGCG intraperitoneal injection by comparing AIDS dementia-like neuronal damage in prophylactic, therapeutic, and combined prophylactic/therapeutic paradigms. We hypothesize that EGCG-treated mice will show significant decreases in AIDS dementia-like neuronal damage when compared to vehicle-treated mice. These data should lay the foundation for further research leading to human trials in the near future. Narrative: The purpose of this project is to investigate if green tea derived EGCG could attenuate AIDS-like neuronal damage in the mouse model. We hypothesize that EGCG-treated mice will show significant decreases in AIDS dementia-like neuronal damage when compared to vehicle-treated mice. These data should lay the foundation for further research leading to human trials in the near future.
描述(由申请人提供):我们的长期目标是开发治疗艾滋病痴呆症的有效药物。该项目的目的是研究绿茶 EGCG(一种已知的信号转导和转录激活 1 (STAT1) 抑制剂)是否可以通过破坏暴露于含有 HIV-1 蛋白 gp120 和 Tat 的 IFN-g 的小鼠中的 STAT1 信号传导来减轻艾滋病样神经元损伤。以促炎细胞因子水平升高为特征的免疫激活状态被广泛认为是导致艾滋病痴呆样神经元损伤的重要因素,而神经元促炎信号传导的关键调节因子是STAT1。 STAT1 激活涉及与脑缺血以及艾滋病痴呆相关的神经元损伤/死亡。此外,其“激活剂”IFN-g 已被证明在 HIV 阳性个体的脑脊液和大脑中均升高。我们的初步研究结果表明,IFN-g 增强了 gp120 和 Tat 的神经毒性作用。此外,这种联合损伤造成的艾滋病痴呆样神经元损伤在 STAT1 缺陷神经元中很大程度上减弱。我们和其他人已经证明,在艾滋病痴呆和中风模型中,用 EGCG 治疗原代神经元可分别减少 STAT1 激活和由此产生的神经元损伤。我们假设 EGCG 治疗将通过抑制 STAT1 来减少艾滋病痴呆样神经元损伤。目标 1 是建立代表艾滋病痴呆中可能表现出的神经元损伤的小鼠模型。目标 2 将描述 STAT1 在介导 IFN-g、gp120 和 Tat 诱导的小鼠神经元损伤中的作用。为此,我们将比较 STAT1 缺陷小鼠与对照小鼠脑室内注射 IFN-g 与 gp120 或 Tat 后的神经元损伤。我们预计 STAT1 缺陷小鼠与对照小鼠相比,艾滋病痴呆样神经元损伤将显着减少。目标 3 将研究在 gp120 或 Tat 存在的情况下,EGCG 对抑制 IFN-g 介导的 STAT1 激活引起的神经元损伤的影响。在这里,我们还计划通过比较预防性、治疗性和联合预防/治疗范例中的艾滋病痴呆样神经元损伤来描述最有效的 EGCG 腹腔注射。我们假设,与媒介物处理的小鼠相比,EGCG 处理的小鼠的艾滋病痴呆样神经元损伤显着减少。这些数据应该为不久的将来进行人体试验的进一步研究奠定基础。叙述:该项目的目的是研究绿茶提取的 EGCG 是否可以减轻小鼠模型中类似艾滋病的神经元损伤。我们假设,与媒介物处理的小鼠相比,EGCG 处理的小鼠的艾滋病痴呆样神经元损伤显着减少。这些数据应该为不久的将来进行人体试验的进一步研究奠定基础。

项目成果

期刊论文数量(5)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Psychiatric implications of hepatitis-C infection.
丙型肝炎感染的精神影响。
  • DOI:
    10.1615/critrevneurobiol.v19.i2-3.20
  • 发表时间:
    2007
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Giunta,Brian;Somboonwit,Charurut;Nikolic,WilliamV;Rrapo,Elona;Tan,Jun;Shapshak,Paul;Fernandez,Francisco
  • 通讯作者:
    Fernandez,Francisco
Antiretroviral medications disrupt microglial phagocytosis of β-amyloid and increase its production by neurons: implications for HIV-associated neurocognitive disorders.
  • DOI:
    10.1186/1756-6606-4-23
  • 发表时间:
    2011-06-07
  • 期刊:
  • 影响因子:
    3.6
  • 作者:
    Giunta B;Ehrhart J;Obregon DF;Lam L;Le L;Jin J;Fernandez F;Tan J;Shytle RD
  • 通讯作者:
    Shytle RD
HIV-1 Tat-induced microglial activation and neuronal damage is inhibited via CD45 modulation: A potential new treatment target for HAND.
HIV-1 Tat 诱导的小胶质细胞激活和神经元损伤通过 CD45 调节受到抑制:HAND 的潜在新治疗靶点。
HIV-1 TAT inhibits microglial phagocytosis of Abeta peptide.
Efavirenz promotes β-secretase expression and increased Aβ1-40,42 via oxidative stress and reduced microglial phagocytosis: implications for HIV associated neurocognitive disorders (HAND).
  • DOI:
    10.1371/journal.pone.0095500
  • 发表时间:
    2014
  • 期刊:
  • 影响因子:
    3.7
  • 作者:
    Brown LA;Jin J;Ferrell D;Sadic E;Obregon D;Smith AJ;Tan J;Giunta B
  • 通讯作者:
    Giunta B
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Jun Tan其他文献

Jun Tan的其他文献

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{{ truncateString('Jun Tan', 18)}}的其他基金

Identification of novel APP-specific alpha secretase in human umbilical cord blood sera
人脐带血血清中新型 APP 特异性 α 分泌酶的鉴定
  • 批准号:
    9380529
  • 财政年份:
    2017
  • 资助金额:
    $ 18.38万
  • 项目类别:
A flavonoid gamma-secretase modulator (GSM) reduces beta-amyloid and tau pathologies in the AD mice
类黄酮 γ 分泌酶调节剂 (GSM) 可减少 AD 小鼠的 β-淀粉样蛋白和 tau 蛋白病理
  • 批准号:
    9127058
  • 财政年份:
    2015
  • 资助金额:
    $ 18.38万
  • 项目类别:
A flavonoid gamma-secretase modulator (GSM) reduces beta-amyloid and tau pathologies in the AD mice
类黄酮 γ 分泌酶调节剂 (GSM) 可减少 AD 小鼠的 β-淀粉样蛋白和 tau 蛋白病理
  • 批准号:
    8976888
  • 财政年份:
    2015
  • 资助金额:
    $ 18.38万
  • 项目类别:
Flavonoid-diosmin modulation of Abeta and tau pathologies through GSK-3 signaling
类黄酮-地奥司明通过 GSK-3 信号传导调节 Abeta 和 tau 病理学
  • 批准号:
    8627446
  • 财政年份:
    2014
  • 资助金额:
    $ 18.38万
  • 项目类别:
Octyl gallate (OG) and Promotion of non-amyloidogenic processing of APP
没食子酸辛酯 (OG) 和促进 APP 的非淀粉样蛋白加工
  • 批准号:
    8803251
  • 财政年份:
    2013
  • 资助金额:
    $ 18.38万
  • 项目类别:
Octyl gallate (OG) and Promotion of non-amyloidogenic processing of APP
没食子酸辛酯 (OG) 和促进 APP 的非淀粉样蛋白加工
  • 批准号:
    8441038
  • 财政年份:
    2013
  • 资助金额:
    $ 18.38万
  • 项目类别:
IL-6-mediated Jak2/Stat3 signaling and Brain Development
IL-6 介导的 Jak2/Stat3 信号传导与大脑发育
  • 批准号:
    7985709
  • 财政年份:
    2010
  • 资助金额:
    $ 18.38万
  • 项目类别:
IL-6-mediated Jak2/Stat3 signaling and Brain Development
IL-6 介导的 Jak2/Stat3 信号传导与大脑发育
  • 批准号:
    8135535
  • 财政年份:
    2010
  • 资助金额:
    $ 18.38万
  • 项目类别:
Implication of HUCBC: a novel therapeutic strategy for Alzheimer's disease
HUCBC 的意义:阿尔茨海默病的一种新治疗策略
  • 批准号:
    8305549
  • 财政年份:
    2009
  • 资助金额:
    $ 18.38万
  • 项目类别:
Implication of HUCBC: a novel therapeutic strategy for Alzheimer's disease
HUCBC 的意义:阿尔茨海默病的一种新治疗策略
  • 批准号:
    8505320
  • 财政年份:
    2009
  • 资助金额:
    $ 18.38万
  • 项目类别:

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