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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

批准号：
8368832
负责人：
M. Maral Mouradian
金额：
$ 17.92万
依托单位：
UNIV OF MED/DENT NJ-R W JOHNSON MED SCH
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-30 至 2013-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8368832
关键词：
Acute Address Adenosine A2A Receptor Age-Months Anti-Inflammatory Agents Anti-inflammatory Apoptosis Attenuated Biochemical Biochemistry Brain Caffeine Cells Charge Chronic Coffee Complex Consumption Cyclic AMP-Dependent Protein Kinases Data Defect Development Dietary Supplementation Diffuse Drosophila genus Epidemiologic Studies Epidemiology Event Exposure to Goals Human In Vitro Link Lipids Mediating Methylation Mitochondria Modeling Modification Molecular Motor Mus Neurodegenerative Disorders Neurons Oxidation-Reduction Oxidative Stress Parkinson Disease Pathology Patients Pharmacologic Substance Phosphoric Monoester Hydrolases Phosphorylation Play Prevalence Protein phosphatase Proteins Receptor Signaling Regulation Reporting Research Risk Rodent Model Role Signal Transduction Source Testing Toxin Transgenic Mice Work base brain cell cell type cost dietary supplements disability disorder risk dopaminergic neuron efficacy testing improved in vivo inhibitor/antagonist killings medical food methyl group mouse model neuroprotection overexpression pre-clinical prevent protective effect protein phosphatase methylesterase-1 research study stem success synuclein synucleinopathy

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。