The Neurosecretory Protein VGF: Contributions to Pain

神经分泌蛋白 VGF:导致疼痛的因素

基本信息

  • 批准号:
    7802914
  • 负责人:
  • 金额:
    $ 22.42万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2009
  • 资助国家:
    美国
  • 起止时间:
    2009-04-15 至 2012-02-28
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): The proposed project will characterize a novel signaling system in the pain pathway. VGF (non-acronymic) is a neurosecretory protein similar to the family of chromogranins. It is sorted in the regulated secretory pathway and proteolytically processed into fragments that are released upon stimulation. Currently the precise identity of VGF bioactive fragments and their mechanisms of action are unknown. Our preliminary studies indicate that VGF is rapidly upregulated in models of neuropathic and inflammatory pain. Furthermore, we have found that a VGF-derived peptide (VGF-C30) induces thermal hyperalgesia following spinal administration. These findings have lead us to hypothesize that VGF is involved in pain signaling under conditions of chronic pain. The objective of the proposed project is to establish foundations for in-depth mechanistic analysis of the role of VGF in chronic pain. Specific Aim 1 will evaluate the physiological relevance of VGF in the pain pathway by addressing the following hypotheses: 1) VGF-derived fragments are released from sensory neurons upon stimulation. In these experiments, VGF fragments released from sensory neurons in a depolarization-dependent manner will be characterized using biochemical approaches, including mass spectrometry. 2) The behavioral effects of VGF- C30 are the result of a receptor-mediated activation of an intracellular signaling pathway. The potential receptors activated by VGF-derived bioactive molecules and their signaling mechanisms are completely uncharacterized. The proposed studies will evaluate the binding site(s) of VGF-C30 in spinal cord membrane preparations pharmacologically and biochemically. In addition, based on preliminary evidence, the contribution of mitogen-activated protein kinase pathways to the mechanisms if VGF-C30 signaling in spinal cord will be examined. Specific Aim 2 will address the hypothesis that VGF contributes to mechanisms of chronic pain. The proposed studies will employ two approaches to address this hypothesis: 1) an already established line of VGF knockout mice, and 2) siRNA-mediated knock-down of VGF expression. The combination of these two approaches will allow comprehensive evaluation of the role of VGF in the development and maintenance of chronic pain. In summary, the proposed project will examine the contribution of a novel signaling system to mechanism of chronic pain. The information gained may establish VGF as a potential therapeutic target for chronic pain conditions. The proposed project will characterize a novel signaling system in the pain pathway: the neurosecretory protein VGF (non-acronymic). These studies will lay the foundations for in-depth mechanistic analysis of the role of VGF in chronic pain. The information gained may establish VGF as a potential therapeutic target for chronic pain conditions.
描述(由申请人提供):拟议项目将描述疼痛通路中的一种新型信号系统。 VGF(非缩写)是一种与嗜铬粒蛋白家族相似的神经分泌蛋白。它在受调节的分泌途径中进行分类,并通过蛋白水解加工成在刺激后释放的片段。目前,VGF 生物活性片段的准确身份及其作用机制尚不清楚。我们的初步研究表明,VGF 在神经性疼痛和炎性疼痛模型中迅速上调。此外,我们发现VGF衍生肽(VGF-C30)在脊髓给药后诱导热痛觉过敏。这些发现使我们推测 VGF 参与慢性疼痛条件下的疼痛信号传导。该项目的目标是为 VGF 在慢性疼痛中的作用的深入机制分析奠定基础。具体目标 1 将通过提出以下假设来评估 VGF 在疼痛通路中的生理相关性:1) VGF 衍生片段在受到刺激时从感觉神经元中释放。在这些实验中,将使用包括质谱在内的生化方法来表征以去极化依赖性方式从感觉神经元释放的 VGF 片段。 2) VGF-C30 的行为效应是受体介导的细胞内信号通路激活的结果。由 VGF 衍生的生物活性分子激活的潜在受体及其信号传导机制完全未知。拟议的研究将从药理学和生物化学角度评估脊髓膜制剂中 VGF-C30 的结合位点。此外,根据初步证据,将检查有丝分裂原激活蛋白激酶途径对脊髓中 VGF-C30 信号传导机制的贡献。具体目标 2 将解决 VGF 有助于慢性疼痛机制的假设。拟议的研究将采用两种方法来解决这一假设:1)已经建立的 VGF 敲除小鼠品系,2)siRNA 介导的 VGF 表达敲低。这两种方法的结合将能够全面评估 VGF 在慢性疼痛的发展和维持中的作用。总之,拟议的项目将研究新型信号系统对慢性疼痛机制的贡献。获得的信息可能会将 VGF 确立为慢性疼痛的潜在治疗靶点。该项目将描述疼痛通路中的一种新型信号系统:神经分泌蛋白 VGF(非缩写)。这些研究将为深入分析 VGF 在慢性疼痛中的作用奠定基础。获得的信息可能会将 VGF 确立为慢性疼痛的潜在治疗靶点。

项目成果

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LYUDMILA H VULCHANOVA其他文献

LYUDMILA H VULCHANOVA的其他文献

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{{ truncateString('LYUDMILA H VULCHANOVA', 18)}}的其他基金

Selective peripheral neuromodulation through organ-specific AAV-mediated gene transfer
通过器官特异性 AAV 介导的基因转移进行选择性周围神经调节
  • 批准号:
    9051168
  • 财政年份:
    2015
  • 资助金额:
    $ 22.42万
  • 项目类别:
TLQP-21 and C3aR, a Novel Receptor/Ligand Interaction in Neuropathic Pain
TLQP-21 和 C3aR,神经性疼痛中的新型受体/配体相互作用
  • 批准号:
    8853350
  • 财政年份:
    2014
  • 资助金额:
    $ 22.42万
  • 项目类别:
TLQP-21 and C3aR, a Novel Receptor/Ligand Interaction in Neuropathic Pain
TLQP-21 和 C3aR,神经性疼痛中的新型受体/配体相互作用
  • 批准号:
    9064237
  • 财政年份:
    2014
  • 资助金额:
    $ 22.42万
  • 项目类别:
TLQP-21 and C3aR, a Novel Receptor/Ligand Interaction in Neuropathic Pain
TLQP-21 和 C3aR,神经性疼痛中的新型受体/配体相互作用
  • 批准号:
    8762837
  • 财政年份:
    2014
  • 资助金额:
    $ 22.42万
  • 项目类别:
TLQP-21 and C3aR, a Novel Receptor/Ligand Interaction in Neuropathic Pain
TLQP-21 和 C3aR,神经性疼痛中的新型受体/配体相互作用
  • 批准号:
    9282731
  • 财政年份:
    2014
  • 资助金额:
    $ 22.42万
  • 项目类别:
The Neurosecretory Protein VGF: Contributions to Pain
神经分泌蛋白 VGF:导致疼痛的因素
  • 批准号:
    7509342
  • 财政年份:
    2009
  • 资助金额:
    $ 22.42万
  • 项目类别:
Combined Proteomic and Functional Analysis of Sensory Neuron Plasticity
感觉神经元可塑性的蛋白质组学和功能联合分析
  • 批准号:
    7286849
  • 财政年份:
    2006
  • 资助金额:
    $ 22.42万
  • 项目类别:
Combined Proteomic and Functional Analysis of Sensory Neuron Plasticity
感觉神经元可塑性的蛋白质组学和功能联合分析
  • 批准号:
    7016574
  • 财政年份:
    2006
  • 资助金额:
    $ 22.42万
  • 项目类别:
Peripheral Mechanisms of Sensory Neuron Plasticity
感觉神经元可塑性的外周机制
  • 批准号:
    7239542
  • 财政年份:
    2004
  • 资助金额:
    $ 22.42万
  • 项目类别:
Peripheral Mechanisms of Sensory Neuron Plasticity
感觉神经元可塑性的外周机制
  • 批准号:
    6881621
  • 财政年份:
    2004
  • 资助金额:
    $ 22.42万
  • 项目类别:

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