Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República, 2780-157, Oeiras, Portugal.
iBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2781-901, Oeiras, Portugal.
Sci Rep. 2018 May 3;8(1):6965. doi: 10.1038/s41598-018-25118-z.
Parkinson's disease (PD) is an age-related neurodegenerative disease associated with the misfolding and aggregation of alpha-synuclein (aSyn). The molecular underpinnings of PD are still obscure, but nutrition may play an important role in the prevention, onset, and disease progression. Dietary (poly)phenols revert and prevent age-related cognitive decline and neurodegeneration in model systems. However, only limited attempts were made to evaluate the impact of digestion on the bioactivities of (poly)phenols and determine their mechanisms of action. This constitutes a challenge for the development of (poly)phenol-based nutritional therapies. Here, we subjected (poly)phenols from Arbutus unedo to in vitro digestion and tested the products in cell models of PD based on the cytotoxicity of aSyn. The (poly)phenol-digested metabolites from A. unedo leaves (LPDMs) effectively counteracted aSyn and HO toxicity in yeast and human cells, improving viability by reducing aSyn aggregation and inducing its clearance. In addition, LPDMs modulated pathways associated with aSyn toxicity, such as oxidative stress, endoplasmic reticulum (ER) stress, mitochondrial impairment, and SIR2 expression. Overall, LPDMs reduced aSyn toxicity, enhanced the efficiency of ER-associated protein degradation by the proteasome and autophagy, and reduced oxidative stress. In total, our study opens novel avenues for the exploitation of (poly)phenols in nutrition and health.
帕金森病（PD）是一种与α-突触核蛋白（aSyn）错误折叠和聚集相关的年龄相关性神经退行性疾病。PD 的分子基础仍不清楚，但营养可能在预防、发病和疾病进展中发挥重要作用。饮食（多）酚类物质可在模型系统中逆转和预防与年龄相关的认知能力下降和神经退行性变。然而，仅有限的尝试评估了消化对（多）酚类生物活性的影响，并确定其作用机制。这对基于（多）酚类的营养疗法的发展构成了挑战。在这里，我们对杨梅中的（多）酚类物质进行了体外消化，并基于 aSyn 的细胞毒性在 PD 细胞模型中测试了产物。杨梅叶（LPDMs）中的（多）酚消化代谢产物可有效拮抗 aSyn 和 HO 毒性，通过减少 aSyn 聚集和诱导其清除来提高酵母和人类细胞的活力。此外，LPDMs 调节了与 aSyn 毒性相关的途径，如氧化应激、内质网（ER）应激、线粒体损伤和 SIR2 表达。总的来说，LPDMs 降低了 aSyn 毒性，增强了蛋白酶体和自噬介导的 ER 相关蛋白降解的效率，并降低了氧化应激。总的来说，我们的研究为（多）酚在营养和健康中的应用开辟了新的途径。
