Healthspan Maintenance and Prevention of Parkinson's-like Phenotypes with Hydroxytyrosol and Oleuropein Aglycone in C. elegans
Healthspan Maintenance and Prevention of Parkinson's-like Phenotypes with Hydroxytyrosol and Oleuropein Aglycone in C. elegans
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DOI：
10.3390/ijms21072588
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发表时间：
2020-04-01
影响因子：
5.6
通讯作者：
Saul, Nadine
中科院分区：
文献类型：
--
作者：
Brunetti, Giovanni;Di Rosa, Gabriele;Saul, Nadine
许多研究强调地中海饮食(MD)在保持健康方面的有益影响，特别是在衰老期间。即使是神经退行性变，这是自然衰老过程的一部分，也是阿尔茨海默氏症和帕金森氏病(PD)等与衰老相关的神经退行性疾病的基础，MD成功地将其作为目标。在这方面，橄榄油及其多酚成分在过去几年受到越来越多的关注。因此，本研究主要关注两种主要的橄榄油多酚--羟基酪醇(HT)和油菜素苷元(OLE)，以及它们对衰老症状的影响，特别是对帕金森病的影响。为了避免长期、昂贵和有伦理争议的实验，已建立的无脊椎动物模式生物秀丽线虫被用来测试HT和OLE治疗。有趣的是，两种多酚都能提高热应激后的存活率，但只有羟色胺能延长非应激条件下的寿命。此外，在老化的蠕虫中，HT和OLE导致运动行为的改善和作为老化标志的自体荧光的减弱。此外，通过使用三种不同的线虫PD模型，HT和OLE被证明：1)增强肌肉中α-突触核蛋白表达或鱼藤酮暴露的蠕虫的运动能力；2)减少肌肉细胞中α-突触核蛋白的积聚；3)防止含有α-突触核蛋白的多巴胺能神经元的神经变性。兴奋作用、抗氧化能力以及蛋白酶体和II相解毒酶的活性增强是这些有益效果的潜在潜在原因。进一步的生物和医学试验是为了评估HT和OLE的全部潜力，并揭示它们的作用模式。
Numerous studies highlighted the beneficial effects of the Mediterranean diet (MD) in maintaining health, especially during ageing. Even neurodegeneration, which is part of the natural ageing process, as well as the foundation of ageing-related neurodegenerative disorders like Alzheimer's and Parkinson's disease (PD), was successfully targeted by MD. In this regard, olive oil and its polyphenolic constituents have received increasing attention in the last years. Thus, this study focuses on two main olive oil polyphenols, hydroxytyrosol (HT) and oleuropein aglycone (OLE), and their effects on ageing symptoms with special attention to PD. In order to avoid long-lasting, expensive, and ethically controversial experiments, the established invertebrate model organism Caenorhabditis elegans was used to test HT and OLE treatments. Interestingly, both polyphenols were able to increase the survival after heat stress, but only HT could prolong the lifespan in unstressed conditions. Furthermore, in aged worms, HT and OLE caused improvements of locomotive behavior and the attenuation of autofluorescence as a marker for ageing. In addition, by using three different C. elegans PD models, HT and OLE were shown i) to enhance locomotion in worms suffering from alpha-synuclein-expression in muscles or rotenone exposure, ii) to reduce alpha-synuclein accumulation in muscles cells, and iii) to prevent neurodegeneration in alpha-synuclein-containing dopaminergic neurons. Hormesis, antioxidative capacities and an activity-boost of the proteasome & phase II detoxifying enzymes are discussed as potential underlying causes for these beneficial effects. Further biological and medical trials are indicated to assess the full potential of HT and OLE and to uncover their mode of action.