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
• 负责人: M. Maral Mouradian
• 金额: $ 30.35万
• 依托单位: RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-30 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8700581
• 关键词: Synergistic; Neuroprotective; Mechanisms; Coffee; Components

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, eicosanoyl-5-hydroxytryptamide (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 1-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.

描述(申请人提供)：咖啡是迄今为止最广泛和最常被消费的草本提取物。大量的流行病学研究表明，喝咖啡可以降低患帕金森氏症(PD)的风险。这种联系被归因于咖啡因，但咖啡不仅仅是咖啡因，而且咖啡因可能具有神经保护作用的发现绝不排除咖啡中的其他成分可能与咖啡因发挥协同作用的可能性。我们最近分离了咖啡中的一种类脂成分，二十烷酰-5-羟色胺(EHT)，并发现它对帕金森病小鼠模型有保护作用。生化和神经病理学分析表明，饮食中补充EHT可降低1-突触核蛋白的磷酸化和聚集性，具有强大的抗炎作用，并对氧化应激具有保护作用。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，但其下游的神经保护机制仍有待建立。这项研究将通过体外生化分析、基于细胞的分子实验和小鼠帕金森病模型的体内研究，阐明咖啡因和EHT介导的神经保护的分子机制及其协同作用。这项工作的最终目标是开发一种膳食补充剂(S)或医疗食品，可以减缓或防止帕金森氏症等神经退行性疾病的发展。