Synergistic Neuroprotective Mechanisms of Coffee Components in Parkinson's Diseas

描述（由申请人提供）：咖啡是迄今为止最广泛和高度消费的草药提取物。许多流行病学研究表明，喝咖啡可以降低患帕金森病（PD）的风险。这种联系归因于咖啡因，但咖啡不仅仅是咖啡因，咖啡因可能对神经有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协同作用的可能性。我们最近从咖啡中分离出一种脂类成分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，膳食中添加EHT可降低？-synuclein磷酸化和聚集，具有强大的抗炎作用，并可防止氧化应激。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。本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对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或医疗食品，以减缓或预防神经退行性疾病（如PD）的发展。

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.