Inhibition of neuronal cell death in Parkinson's disease by transduction of neurotrophic factor gene.

通过神经营养因子基因转导抑制帕金森病中的神经细胞死亡。

基本信息

  • 批准号:
    11670640
  • 负责人:
  • 金额:
    $ 1.34万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
  • 财政年份:
    1999
  • 资助国家:
    日本
  • 起止时间:
    1999 至 2000
  • 项目状态:
    已结题

项目摘要

Pigment epithelium-derived factor (PEDF), a neurotrophic agents first identified in conditioned medium from cultured human retinal pigment epithelial cells, induces neuronal differentiation with neuritic outgrowth in Y-79 retinoblastoma cells and has a neurotrophic survival effect on cerebellar granule cells in culture. PEDF also have protective effect against glutamate toxicity and induction of apoptotic cell death of cultured granular cells. In this project, first we investigated the effects of human recombinant PEDF (hrPEDF) on proliferation of cultured nigral neurones. To do this experiments, we used cultures of nigral neurones isolated from the fetal rat brains. The number of nigral neurones, which identified by immunohistochemistry for tyrosine hydroxilase, is larger in the presence of PEDF than that of controls. The effect of PEDF showed a dose-response relationship. In second studies, we have performed the transduction of PEDF gene to the striatum and nigra of mice. To this purpose, we used recombinent adeno-associated (AAV) vectors which are sufficient for packaging and integration. AAV containing cDNA encoding PEDF and GFP were injected to the striatum of the mice by streotaxic operation. GFP-positive cells were observed in the striatum and the substantia nigra, which were transported through strionigral pathway. We are now conducting immunohistochemistry for PEDF on these sections to confirm the expression of the PEDF.Our study suggest the possibility of PEDF gene transfer to the striatum and nigra and effect of survival of niral neurones, and furthermore potential role for the gene therapy of Parkinson's disease
色素上皮衍生因子(PEDF)是一种神经营养因子,在培养的人视网膜色素上皮细胞的条件培养液中首次发现,它能诱导Y-79视网膜母细胞瘤细胞向神经元分化并产生神经炎样生长,对培养的小脑颗粒细胞具有神经营养存活作用。PEDF对谷氨酸毒性和诱导颗粒细胞凋亡也有保护作用。在本研究中,我们首先研究了人重组PEDF(hrPEDF)对培养的黑质神经元增殖的影响。为了做这个实验,我们使用了从胎鼠大脑中分离的黑质神经元的培养物。酪氨酸羟化酶免疫组化结果显示,PEDF组黑质神经元的数量明显多于对照组。PEDF的作用呈剂量-反应关系。在第二个研究中,我们进行了PEDF基因转导到小鼠的纹状体和黑质。为此目的,我们使用重组腺相关(AAV)载体,其足以进行包装和整合。将含有编码PEDF和GFP的cDNA的AAV注射到小鼠的纹状体中。在纹状体和黑质中观察到GFP阳性细胞,其通过纹状体黑质途径转运。本研究旨在探讨PEDF基因转移到纹状体和黑质的可能性及其对神经元存活的影响,并为帕金森病的基因治疗奠定基础

项目成果

期刊论文数量(16)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Mizuno Y, Hattori N, Mori H: "Genetics of Parkinson's disease."Biomed Pharmacother. 53. 109-116 (1999)
Mizuno Y、Hattori N、Mori H:“帕金森病的遗传学”。Biomed Pharmacother。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Mizuno Y,Hattori N,Mori H: "Genetics of Parkinson's desease"Biomed Phormacother. 59. 109-116 (1999)
Mizuno Y,Hattori N,Mori H:“帕金森病的遗传学”Biomed Phormacother。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Sugita Y, Zhao B, Shankar P, Dunbar CE, Doren S, Young HA, Schwartz JP: "CNS interleukin-3 (IL-3) expression and neurological syndrome in antisense-IL-3 transgenic mice."J Neuropathol Exp Neurol. 58. 480-8 (1999)
Sugita Y、Zhao B、Shankar P、Dunbar CE、Doren S、Young HA、Schwartz JP:“反义 IL-3 转基因小鼠中的中枢神经系统白细胞介素 3 (IL-3) 表达和神经系统综合征。”J Neuropathol Exp Neurol。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Sugita Y,Zhao B,Shankar P,Dunbar CE,Doren S,Young HA,Schwartz JP: "CNS interleukin-3(IL-3) expression and neurological syndrome in antisense-IL-3 transgenic mice."J Neuropathol Exp Neurol. 58. 480-488 (1999)
Sugita Y、Zhao B、Shankar P、Dunbar CE、Doren S、Young HA、Schwartz JP:“反义 IL-3 转基因小鼠中枢神经系统白细胞介素 3 (IL-3) 的表达和神经系统综合征。”J Neuropathol Exp Neurol。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Takanashi M,Mochizuki H,Yokomizo K,Hattori N,Mori H,et al.: "Iron accumulation in the substantia nigra of autosomal recessive javenile parkinsonism"Parkinson's disease and related disorders. in press.
Takanashi M,Mochizuki H,Yokomizo K,Hattori N,Mori H,et al.:“常染色体隐性青少年帕金森病黑质中的铁积累”帕金森病和相关疾病。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
{{ 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 }}

MORI Hideo其他文献

MORI Hideo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('MORI Hideo', 18)}}的其他基金

EFD Analysis of complex flow fields by measurement of pressure distribution based on lifetime imaging
基于寿命成像的压力分布测量 EFD 分析复杂流场
  • 批准号:
    19K04171
  • 财政年份:
    2019
  • 资助金额:
    $ 1.34万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Development of high-sensitive measurement system of pressure distribution by pressure-sensitive coatings with new technology
新技术开发压敏涂层高灵敏压力分布测量系统
  • 批准号:
    15K13874
  • 财政年份:
    2015
  • 资助金额:
    $ 1.34万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
Boiling Heat Transfer in Small FlowChannels and its Enhancement Mechanism
小流量通道内沸腾传热及其强化机理
  • 批准号:
    22560201
  • 财政年份:
    2010
  • 资助金额:
    $ 1.34万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Imaging Analysis of Turbomachinery Internal Flows Using Pressure and Temperature Sensitive Paints
使用压力和温度敏感涂料对涡轮机械内部流动进行成像分析
  • 批准号:
    21760134
  • 财政年份:
    2009
  • 资助金额:
    $ 1.34万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
Development of an Analysis Model for Thermal Hydraulics on a Liquid and Gas Two-phase Flow through a Microscale Porous Material
微尺度多孔材料液气两相流热水力学分析模型的开发
  • 批准号:
    18560206
  • 财政年份:
    2006
  • 资助金额:
    $ 1.34万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Studies on the practical diagnosis and pathomechanism of tauopathy as neurodegenerative disordrs
神经退行性疾病 tau 蛋白病的实际诊断和病理机制研究
  • 批准号:
    16590848
  • 财政年份:
    2004
  • 资助金额:
    $ 1.34万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Transient Heat Transfer in a Tube during Pressure Reduction from Supercritical to Subcritical Pressure
从超临界压力降至亚临界压力期间管内的瞬态传热
  • 批准号:
    16560188
  • 财政年份:
    2004
  • 资助金额:
    $ 1.34万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Investigation of mechanism of tauopathy and application for clinical diagnosis
tau蛋白病机制研究及临床诊断应用
  • 批准号:
    13670667
  • 财政年份:
    2001
  • 资助金额:
    $ 1.34万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
RESEARCH AND DEVELOPMENT OF ROBOTIC TRAVEL AID FOR THE BLIND
盲人出行机器人研发
  • 批准号:
    12555071
  • 财政年份:
    2000
  • 资助金额:
    $ 1.34万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Prediction Model of Heat and Mass Transfer in Metal Hydride Packed Beds
金属氢化物填充床传热传质预测模型
  • 批准号:
    12650210
  • 财政年份:
    2000
  • 资助金额:
    $ 1.34万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)

相似海外基金

The effect of brain derived neurotrophic factor on presynaptic function
脑源性神经营养因子对突触前功能的影响
  • 批准号:
    10534078
  • 财政年份:
    2022
  • 资助金额:
    $ 1.34万
  • 项目类别:
Signaling mechanisms of the pro Brain Derived Neurotrophic Factor (proBDNF) and the prodomain BDNF (pBDNF) in neurons
神经元中前脑源性神经营养因子 (proBDNF) 和前结构域 BDNF (pBDNF) 的信号传导机制
  • 批准号:
    RGPIN-2021-02498
  • 财政年份:
    2022
  • 资助金额:
    $ 1.34万
  • 项目类别:
    Discovery Grants Program - Individual
The association between brain-derived neurotrophic factor gene polymorphisms and Parkinson's disease: Analysis of the Canadian Longitudinal Study on Aging
脑源性神经营养因子基因多态性与帕金森病的关联:加拿大衰老纵向研究分析
  • 批准号:
    460145
  • 财政年份:
    2022
  • 资助金额:
    $ 1.34万
  • 项目类别:
Elucidation of the pathogenesis and new therapeutic strategies for brain- and gut-related steatohepatitis based on brain-derived neurotrophic factor
基于脑源性神经营养因子阐明脑和肠道相关脂肪性肝炎的发病机制和新的治疗策略
  • 批准号:
    22K07024
  • 财政年份:
    2022
  • 资助金额:
    $ 1.34万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Brain-Derived Neurotrophic Factor in hemostasis and thrombosis
脑源性神经营养因子在止血和血栓形成中的作用
  • 批准号:
    461179
  • 财政年份:
    2022
  • 资助金额:
    $ 1.34万
  • 项目类别:
    Operating Grants
The effect of brain derived neurotrophic factor on presynaptic function
脑源性神经营养因子对突触前功能的影响
  • 批准号:
    10685272
  • 财政年份:
    2022
  • 资助金额:
    $ 1.34万
  • 项目类别:
Effects of chemogenetic inhibition of astrocytes on pattern separation and brain-derived neurotrophic factor levels
星形胶质细胞化学遗传学抑制对模式分离和脑源性神经营养因子水平的影响
  • 批准号:
    575689-2022
  • 财政年份:
    2022
  • 资助金额:
    $ 1.34万
  • 项目类别:
    Alexander Graham Bell Canada Graduate Scholarships - Master's
Study of the mechanism of action of a new neurotrophic factor subtype BDNF propeptide
新型神经营养因子亚型BDNF前肽作用机制研究
  • 批准号:
    22K06448
  • 财政年份:
    2022
  • 资助金额:
    $ 1.34万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Blood-brain Barrier Permeability to the Platelet-secreted Brain-derived Neurotrophic Factor (BDNF)
血脑屏障对血小板分泌的脑源性神经营养因子 (BDNF) 的通透性
  • 批准号:
    459136
  • 财政年份:
    2021
  • 资助金额:
    $ 1.34万
  • 项目类别:
    Studentship Programs
Signaling mechanisms of the pro Brain Derived Neurotrophic Factor (proBDNF) and the prodomain BDNF (pBDNF) in neurons
神经元中前脑源性神经营养因子 (proBDNF) 和前结构域 BDNF (pBDNF) 的信号传导机制
  • 批准号:
    DGECR-2021-00015
  • 财政年份:
    2021
  • 资助金额:
    $ 1.34万
  • 项目类别:
    Discovery Launch Supplement
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了