Mancini Ross S, Wang Yanfei, Weaver Donald F
Department of Fundamental Neurobiology, Krembil Research Institute, University Health Network, Toronto, ON, Canada.
Department of Chemistry, University of Toronto, Toronto, ON, Canada.
Front Neurosci. 2018 Oct 12;12:735. doi: 10.3389/fnins.2018.00735. eCollection 2018.
Coffee consumption has been correlated with a decreased risk of developing Alzheimer's disease (AD) and Parkinson's disease (PD), but the mechanism by which coffee may provide neuroprotection in humans is not fully understood. We hypothesized that compounds found in brewed coffee may elicit neuroprotective effects by inhibiting the aggregation of amyloid-beta (Aβ) and tau (AD) or α-synuclein (PD). Three instant coffee extracts (light roast, dark roast, decaffeinated dark roast) and six coffee components [caffeine (), chlorogenic acid (), quinic acid (), caffeic acid (), quercetin (), and phenylindane ()] were investigated for their ability to inhibit the fibrillization of Aβ and tau proteins using thioflavin T (ThT) and thioflavin S (ThS) fluorescence assays, respectively. Inhibition of Aβ and α-synuclein oligomerization was assessed using ELISA assays. All instant coffee extracts inhibit fibrillization of Aβ and tau, and promote α-synuclein oligomerization at concentrations above 100 μg/mL. Dark roast coffee extracts are more potent inhibitors of Aβ oligomerization (IC ca. 10 μg/mL) than light roast coffee extract (IC = 40.3 μg/mL), and pure caffeine () has no effect on Aβ, tau or α-synuclein aggregation. Coffee components , and inhibit the fibrillization of Aβ at 100 μM concentration, yet only inhibits Aβ oligomerization (IC = 10.3 μM). - have no effect on tau fibrillization. Coffee component , however, is a potent inhibitor of both Aβ and tau fibrillization, and also inhibits Aβ oligomerization (IC = 42.1 μM). Coffee components and promote the aggregation of α-synuclein at concentrations above 100 μM; no other coffee components affect α-synuclein oligomerization. While the neuroprotective effect of coffee consumption is likely due to a combination of factors, our data suggest that inhibition Aβ and tau aggregation by phenylindane (formed during the roasting of coffee beans, higher quantities found in dark roast coffees) is a plausible mechanism by which coffee may provide neuroprotection. The identification of as a dual-inhibitor of both Aβ and tau aggregation is noteworthy, and to our knowledge this is the first report of the aggregation inhibition activity of .
咖啡消费与患阿尔茨海默病（AD）和帕金森病（PD）风险降低相关，但咖啡对人类提供神经保护的机制尚未完全了解。我们推测，煮制咖啡中发现的化合物可能通过抑制淀粉样β蛋白（Aβ）和tau蛋白（AD）或α-突触核蛋白（PD）的聚集而产生神经保护作用。使用硫黄素T（ThT）和硫黄素S（ThS）荧光测定法，分别研究了三种速溶咖啡提取物（浅度烘焙、深度烘焙、脱咖啡因深度烘焙）和六种咖啡成分[咖啡因（）、绿原酸（）、奎尼酸（）、咖啡酸（）、槲皮素（）和苯基茚满（）]抑制Aβ和tau蛋白纤维化的能力。使用酶联免疫吸附测定（ELISA）评估Aβ和α-突触核蛋白寡聚化的抑制情况。所有速溶咖啡提取物在浓度高于100μg/mL时均抑制Aβ和tau的纤维化，并促进α-突触核蛋白寡聚化。深度烘焙咖啡提取物比浅度烘焙咖啡提取物（IC = 40.3μg/mL）对Aβ寡聚化的抑制作用更强（IC约为10μg/mL），而纯咖啡因（）对Aβ、tau或α-突触核蛋白聚集没有影响。咖啡成分、和在100μM浓度时抑制Aβ的纤维化，但只有抑制Aβ寡聚化（IC = 10.3μM）。 - 对tau纤维化没有影响。然而，咖啡成分是Aβ和tau纤维化的有效抑制剂，也抑制Aβ寡聚化（IC = 42.1μM）。咖啡成分和在浓度高于100μM时促进α-突触核蛋白的聚集；没有其他咖啡成分影响α-突触核蛋白寡聚化。虽然咖啡消费的神经保护作用可能是多种因素共同作用的结果，但我们的数据表明，苯基茚满（在咖啡豆烘焙过程中形成，在深度烘焙咖啡中含量更高）抑制Aβ和tau聚集是咖啡可能提供神经保护的一种合理机制。作为Aβ和tau聚集的双重抑制剂的鉴定值得注意，据我们所知，这是关于的聚集抑制活性的首次报道。
