Departmento de Nutrición y Bromatología, Toxicología y Medicina Legal, Área de Nutrición y Bromatología, Facultad de Farmacia, Universidad de Sevilla, C/Profesor García González, 2. 41012, Sevilla, Spain.
Departmento de Nutrición y Bromatología, Toxicología y Medicina Legal, Área de Nutrición y Bromatología, Facultad de Farmacia, Universidad de Sevilla, C/Profesor García González, 2. 41012, Sevilla, Spain.
Food Chem Toxicol. 2018 Oct;120:41-49. doi: 10.1016/j.fct.2018.06.059. Epub 2018 Jun 30.
There is a considerable consensus that the increased production and/or aggregation of α-synuclein (αsyn) plays a central role in the pathogenesis of Parkinson's disease (PD). Therefore, a method of identifying molecules that block αsyn aggregation and prevent the loss of dopaminergic neurons is urgently needed in order to treat or slow the progression of PD. Hydroxytyrosol (HT), a well-known bioactive food compound present in olive oil, olives and wine, possesses demonstrated antioxidant and anti-inflammatory properties that can cross the Blood Brain Barrier (BBB). In the present work, the role of HT, tyrosol (TYR) and other tyrosine metabolites (hydroxyphenyl acetic acid (HPAA)) against αsyn aggregation, destabilisation and toxicity was evaluated through the use of different in vitro tests (Thioflavin T (ThT), Transmission Electronic Microscopy (TEM), electrophoresis and MTT assay). Results show that HT presents a strong inhibitory effect preventing αsyn aggregation and exercising a destabilising effect by disaggregating αsyn fibrils. Moreover, HT is able to counteract αsyn-induced toxicity. This is the first time that the effect of HT against αsyn toxicity and aggregation is evaluated. Thus, HT can be considered a promising compound for further approaches to tackling PD.
人们普遍认为，α-突触核蛋白（αsyn）的产量增加和/或聚集在帕金森病（PD）的发病机制中起着核心作用。因此，迫切需要一种识别能够阻止αsyn 聚集并防止多巴胺能神经元丢失的分子的方法，以便治疗或减缓 PD 的进展。羟基酪醇（HT）是橄榄油、橄榄和葡萄酒中一种众所周知的具有生物活性的食物化合物，具有已被证明的抗氧化和抗炎特性，可穿透血脑屏障（BBB）。在本工作中，通过使用不同的体外试验（硫黄素 T（ThT）、透射电子显微镜（TEM）、电泳和 MTT 测定），评估了 HT、酪醇（TYR）和其他酪氨酸代谢物（对羟基苯乙酸（HPAA））对 αsyn 聚集、失稳和毒性的作用。结果表明，HT 具有很强的抑制作用，可阻止 αsyn 聚集，并通过解聚 αsyn 纤维发挥不稳定作用。此外，HT 能够抵抗 αsyn 诱导的毒性。这是首次评估 HT 对 αsyn 毒性和聚集的作用。因此，HT 可以被认为是进一步治疗 PD 的有前途的化合物。
