Synergistic Neuroprotective Mechanisms of Coffee Components in Parkinson's Diseas

咖啡成分对帕金森病的协同神经保护机制

基本信息

项目摘要

DESCRIPTION (provided by applicant): Coffee is by far the most widely and highly consumed herbal extract. Numerous epidemiological studies indicate that coffee consumption affords reduced risk of Parkinson's disease (PD). This association has been attributed to caffeine, but coffee is much more than just caffeine and the finding that caffeine may be neuroprotective in no way obviates the possibility that other components in coffee may play a synergistic role with caffeine. We have recently isolated a lipid-like component of coffee, EHT, and found it to have a protective effect in mouse models of PD. Biochemical and neuropathological analyses demonstrate that dietary supplementation with EHT leads to decreased ?-synuclein phosphorylation and aggregation, a robust anti-inflammatory effect, and protection against oxidative stress. Studies indicate that the actions of caffeine stem from its antagonism of adenosine A2A receptor signaling, but downstream neuroprotective mechanisms remain to be established. The proposed research will elucidate the molecular mechanisms of neuroprotection mediated by caffeine and EHT as well as their synergy through in vitro biochemical analyses, cell based molecular experiments and in vivo studies in mouse models of PD. The ultimate goal of this work is to develop a dietary supplement(s) or medical food that would slow the progression or prevent the development of neurodegenerative disorders such as PD. PUBLIC HEALTH RELEVANCE: Coffee, which by far is the most widely and highly consumed herbal extract worldwide, has been linked to reduced risk of developing Parkinson's disease. While this effect has been attributed largely to caffeine, coffee has many more components than just caffeine. This project focuses on understanding the mechanisms by which certain coffee constituents protect brain cells. The ultimate goal of this work is to develop a dietary supplement(s) that would slow the progression or prevent the development of neurodegenerative disorders including Parkinson's disease.
描述(由申请人提供):咖啡是迄今为止最广泛和最高消费的草药提取物。许多流行病学研究表明,喝咖啡可以降低帕金森病(PD)的风险。这种关联被归因于咖啡因,但咖啡不仅仅是咖啡因,咖啡因可能具有神经保护作用的发现并不能排除咖啡中其他成分可能与咖啡因发挥协同作用的可能性。我们最近分离出了咖啡中的一种脂质成分EHT,并发现它在PD小鼠模型中具有保护作用。生化和神经病理学分析表明,膳食补充EHT导致?突触核蛋白的磷酸化和聚集,一个强大的抗炎作用,并保护免受氧化应激。研究表明,咖啡因的作用源于其对腺苷A2A受体信号的拮抗作用,但下游的神经保护机制仍有待建立。该研究将通过体外生化分析、细胞分子实验和PD小鼠模型的体内研究,阐明咖啡因和EHT介导的神经保护的分子机制以及它们的协同作用。这项工作的最终目标是开发一种膳食补充剂或医疗食品,以减缓或预防神经退行性疾病(如PD)的发展。 公共卫生关系:咖啡是迄今为止世界上最广泛和最高消费的草药提取物,与降低患帕金森病的风险有关。虽然这种效果主要归因于咖啡因,但咖啡的成分远不止咖啡因。该项目的重点是了解某些咖啡成分保护脑细胞的机制。这项工作的最终目标是开发一种膳食补充剂,可以减缓或预防神经退行性疾病(包括帕金森病)的发展。

项目成果

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M. Maral Mouradian其他文献

M. Maral Mouradian的其他文献

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{{ truncateString('M. Maral Mouradian', 18)}}的其他基金

PME-1: Pathogenetic Role and Therapeutic Opportunity in Neurodegenerative Mixed Proteinopathies
PME-1:神经退行性混合蛋白病的致病作用和治疗机会
  • 批准号:
    10595891
  • 财政年份:
    2023
  • 资助金额:
    $ 17.92万
  • 项目类别:
Alzheimer’s Disease Protection by Reduced Adenylyl Cyclase Type 5
通过减少 5 型腺苷酸环化酶来预防阿尔茨海默病
  • 批准号:
    10526756
  • 财政年份:
    2022
  • 资助金额:
    $ 17.92万
  • 项目类别:
Role of Transglutaminase 2 in Synucleinopathies
转谷氨酰胺酶 2 在突触核蛋白病中的作用
  • 批准号:
    10285001
  • 财政年份:
    2021
  • 资助金额:
    $ 17.92万
  • 项目类别:
Training in Translating Neuroscience to Therapies
将神经科学转化为治疗的培训
  • 批准号:
    10442401
  • 财政年份:
    2021
  • 资助金额:
    $ 17.92万
  • 项目类别:
Training in Translating Neuroscience to Therapies
将神经科学转化为治疗的培训
  • 批准号:
    10204266
  • 财政年份:
    2021
  • 资助金额:
    $ 17.92万
  • 项目类别:
Training in Translating Neuroscience to Therapies
将神经科学转化为治疗的培训
  • 批准号:
    10621360
  • 财政年份:
    2021
  • 资助金额:
    $ 17.92万
  • 项目类别:
PP2A Dysregulation in the Pathogenesis of alpha-Synucleinopathies
α-突触核蛋白病发病机制中的 PP2A 失调
  • 批准号:
    9920223
  • 财政年份:
    2017
  • 资助金额:
    $ 17.92万
  • 项目类别:
Manipulating Gene Expression in the Dyskinesias of Parkinson's Disease
操纵帕金森病运动障碍中的基因表达
  • 批准号:
    9305587
  • 财政年份:
    2016
  • 资助金额:
    $ 17.92万
  • 项目类别:
Synergistic Neuroprotective Mechanisms of Coffee Components in Parkinson's Diseas
咖啡成分对帕金森病的协同神经保护机制
  • 批准号:
    8700581
  • 财政年份:
    2012
  • 资助金额:
    $ 17.92万
  • 项目类别:
Synergistic Neuroprotective Mechanisms of Coffee Components in Parkinson's Diseas
咖啡成分对帕金森病的协同神经保护机制
  • 批准号:
    8543640
  • 财政年份:
    2012
  • 资助金额:
    $ 17.92万
  • 项目类别:

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