PTEN Anti-Oncogene: Neuronal Function and Toxicity

PTEN 抗癌基因:神经元功能和毒性

基本信息

  • 批准号:
    6821785
  • 负责人:
  • 金额:
    $ 14.58万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2004
  • 资助国家:
    美国
  • 起止时间:
    2004-08-15 至 2009-03-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): The PTEN anti-oncogene is among the most frequently mutated genes in malignant brain tumors. Normally, PTEN is a lipid phosphatase which blocks malignant phenotypes primarily by inhibiting the PI3 Kinase/AKT pathways, but PTEN can also act as a protein phosphatase. PTEN is expressed in brain late in development, and neuronal expression continues throughout adult life. Although loss of PTEN can cause neuronal hyperplasia, little is known about the role of PTEN in neuronal development or in normal neurons. Pathways influenced by PTEN suggest that this anti-oncogene may increase neuronal sensitivity to toxicity and/or degenerative processes, which is supported by our preliminary data. This proposal will first determine whether PTEN can modulate sensitivity of cultured neuron-like cells to toxins used in models of Alzheimer's disease and Parkinson's disease. While studying this hypothesis, we have unexpectedly found that PTEN blocks NGF signaling in PC12 cells, and this appears to be at least partially due to inhibition of expression of trkA and p75 NGF receptors at the protein and mRNA levels. DNA microarray then revealed that PTEN can inhibit expression of several genes, including tyrosine hydroxylase and GTP cyclohydrolase 1. Since this may also have implications for neuronal function and for Parkinson's disease, the second Aim of this proposal will also explore the mechanism by which PTEN inhibits expression of these genes. The final Aim of this proposal will explore the effect of age and neurotoxins used in models of neurodegenerative disorders on PTEN levels and function to determine the biological relevance of data generated from the first two Aims. These studies and my development as an independent clinical scientist will be significantly advanced by Dr. M. Flint Beal, who will serve as my sponsor and who is a leading expert in neuronal degeneration in PD and AD. Additional mentoring by Dr. Eric Holland, a leading expert on anti-oncogene signal transduction, will also add significantly to my scientific growth and will also help me to realize many of the Specific Aims of this proposal. The environment at Cornell and the strong support of my institution will permit me to focus upon these studies with minimal distractions. My scientific background is substantial, and this will facilitate realization of the goal of this project. This plan outlined in this award will, however, enhance previously underserved aspects of my education while focusing on an important scientific question, in order to promote a successful transition to scientific independence.
描述(由申请人提供):PTEN抗癌基因是恶性脑肿瘤中最常见的突变基因之一。正常情况下,PTEN是一种脂质磷酸酶,主要通过抑制PI3激酶/AKT通路来阻断恶性表型,但PTEN也可以作为一种蛋白磷酸酶。PTEN在发育后期在大脑中表达,并且在整个成年期神经元中持续表达。尽管PTEN的缺失可导致神经元增生,但对于PTEN在神经元发育或正常神经元中的作用知之甚少。受PTEN影响的通路表明,这种抗癌基因可能增加神经元对毒性和/或退行性过程的敏感性,我们的初步数据支持这一点。该方案将首先确定PTEN是否可以调节培养的神经元样细胞对阿尔茨海默病和帕金森病模型中使用的毒素的敏感性。在研究这一假设时,我们意外地发现PTEN在PC12细胞中阻断NGF信号传导,这似乎至少部分是由于在蛋白和mRNA水平上抑制trkA和p75 NGF受体的表达。DNA芯片显示,PTEN可以抑制酪氨酸羟化酶和GTP环水解酶等基因的表达

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

MICHAEL G KAPLITT其他文献

MICHAEL G KAPLITT的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('MICHAEL G KAPLITT', 18)}}的其他基金

XIAP Gene Therapy in Huntington's Disease
亨廷顿病的 XIAP 基因治疗
  • 批准号:
    8022829
  • 财政年份:
    2010
  • 资助金额:
    $ 14.58万
  • 项目类别:
XIAP Gene Therapy in Huntington's Disease
亨廷顿病的 XIAP 基因治疗
  • 批准号:
    8580861
  • 财政年份:
    2010
  • 资助金额:
    $ 14.58万
  • 项目类别:
XIAP Gene Therapy in Huntington's Disease
亨廷顿病的 XIAP 基因治疗
  • 批准号:
    7774622
  • 财政年份:
    2010
  • 资助金额:
    $ 14.58万
  • 项目类别:
XIAP Gene Therapy in Huntington's Disease
亨廷顿病的 XIAP 基因治疗
  • 批准号:
    8232118
  • 财政年份:
    2010
  • 资助金额:
    $ 14.58万
  • 项目类别:
XIAP Gene Therapy in Huntington's Disease
亨廷顿病的 XIAP 基因治疗
  • 批准号:
    8436248
  • 财政年份:
    2010
  • 资助金额:
    $ 14.58万
  • 项目类别:
Neuroprotection via XIAP gene therapy in Huntington's disease
通过 XIAP 基因治疗对亨廷顿病进行神经保护
  • 批准号:
    7230084
  • 财政年份:
    2006
  • 资助金额:
    $ 14.58万
  • 项目类别:
Neuroprotection via XIAP gene therapy in Huntington's disease
通过 XIAP 基因治疗对亨廷顿病进行神经保护
  • 批准号:
    7076473
  • 财政年份:
    2006
  • 资助金额:
    $ 14.58万
  • 项目类别:
PTEN Anti-Oncogene Influences on Neuronal Function & Toxicity
PTEN 抗癌基因对神经元功能的影响
  • 批准号:
    6937259
  • 财政年份:
    2004
  • 资助金额:
    $ 14.58万
  • 项目类别:
PTEN Anti-Oncogene Influences on Neuronal Function & Toxicity
PTEN 抗癌基因对神经元功能的影响
  • 批准号:
    7103471
  • 财政年份:
    2004
  • 资助金额:
    $ 14.58万
  • 项目类别:
PTEN Anti-Oncogene Influences on Neuronal Function & Toxicity
PTEN 抗癌基因对神经元功能的影响
  • 批准号:
    7391290
  • 财政年份:
    2004
  • 资助金额:
    $ 14.58万
  • 项目类别:

相似国自然基金

新型F-18标记香豆素衍生物PET探针的研制及靶向Alzheimer's Disease 斑块显像研究
  • 批准号:
    81000622
  • 批准年份:
    2010
  • 资助金额:
    20.0 万元
  • 项目类别:
    青年科学基金项目
阿尔茨海默病(Alzheimer's disease,AD)动物模型构建的分子机理研究
  • 批准号:
    31060293
  • 批准年份:
    2010
  • 资助金额:
    26.0 万元
  • 项目类别:
    地区科学基金项目
跨膜转运蛋白21(TMP21)对引起阿尔茨海默病(Alzheimer'S Disease)的γ分泌酶的作用研究
  • 批准号:
    30960334
  • 批准年份:
    2009
  • 资助金额:
    22.0 万元
  • 项目类别:
    地区科学基金项目

相似海外基金

Pathophysiological mechanisms of hypoperfusion in mouse models of Alzheimer?s disease and small vessel disease
阿尔茨海默病和小血管疾病小鼠模型低灌注的病理生理机制
  • 批准号:
    10657993
  • 财政年份:
    2023
  • 资助金额:
    $ 14.58万
  • 项目类别:
Social Connectedness and Communication in Parents with Huntington''s Disease and their Offspring: Associations with Psychological and Disease Progression
患有亨廷顿病的父母及其后代的社会联系和沟通:与心理和疾病进展的关联
  • 批准号:
    10381163
  • 财政年份:
    2022
  • 资助金额:
    $ 14.58万
  • 项目类别:
The Role of Menopause-Driven DNA Damage and Epigenetic Dysregulation in Alzheimer s Disease
更年期驱动的 DNA 损伤和表观遗传失调在阿尔茨海默病中的作用
  • 批准号:
    10531959
  • 财政年份:
    2022
  • 资助金额:
    $ 14.58万
  • 项目类别:
The Role of Menopause-Driven DNA Damage and Epigenetic Dysregulation in Alzheimer s Disease
更年期驱动的 DNA 损伤和表观遗传失调在阿尔茨海默病中的作用
  • 批准号:
    10700991
  • 财政年份:
    2022
  • 资助金额:
    $ 14.58万
  • 项目类别:
Interneurons as early drivers of Huntington´s disease progression
中间神经元是亨廷顿病进展的早期驱动因素
  • 批准号:
    10518582
  • 财政年份:
    2022
  • 资助金额:
    $ 14.58万
  • 项目类别:
Interneurons as Early Drivers of Huntington´s Disease Progression
中间神经元是亨廷顿病进展的早期驱动因素
  • 批准号:
    10672973
  • 财政年份:
    2022
  • 资助金额:
    $ 14.58万
  • 项目类别:
Social Connectedness and Communication in Parents with Huntington''s Disease and their Offspring: Associations with Psychological and Disease Progression
患有亨廷顿病的父母及其后代的社会联系和沟通:与心理和疾病进展的关联
  • 批准号:
    10585925
  • 财政年份:
    2022
  • 资助金额:
    $ 14.58万
  • 项目类别:
Oligodendrocyte heterogeneity in Alzheimer' s disease
阿尔茨海默病中的少突胶质细胞异质性
  • 批准号:
    10180000
  • 财政年份:
    2021
  • 资助金额:
    $ 14.58万
  • 项目类别:
Serum proteome analysis of Alzheimer´s disease in a population-based longitudinal cohort study - the AGES Reykjavik study
基于人群的纵向队列研究中阿尔茨海默病的血清蛋白质组分析 - AGES 雷克雅未克研究
  • 批准号:
    10049426
  • 财政年份:
    2021
  • 资助金额:
    $ 14.58万
  • 项目类别:
Repurposing drugs for Alzheimer´s disease using a reverse translational approach
使用逆翻译方法重新利用治疗阿尔茨海默病的药物
  • 批准号:
    10295809
  • 财政年份:
    2021
  • 资助金额:
    $ 14.58万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了