Parkinson's disease (PD) is a progressive neurodegenerative disease with no satisfactory therapy options. Similar to other neurodegenerative conditions, such as Alzheimer's and Huntington's diseases, oxidative stress plays a key factor in the neurodegeneration process. To counteract the uncontrolled increase of reactive oxygen species (ROS) and oxidative stress-dependent cell death, several preclinical and clinical tests exploit natural-derived organic antioxidants, such as polyphenols. Despite some promising results, free antioxidants show scarce brain accumulation and may exhaust their scavenging activity before reaching the brain. In this work, we developed an antioxidant therapeutic nanoplatform consisting of nano-sized functionalized liposomes loaded with selected polyphenol-rich vegetal extracts with high blood–brain barrier crossing capabilities. The antioxidant extracts were obtained from the grape seeds and skins as a byproduct of wine production (i.e., pomace), following a sustainable circular approach with reduced environmental impact. The antioxidant nanoplatform was successfully tested in a relevant in vitro model of PD, where it completely rescued the ROS levels, prevented the aggregation of α-synuclein fibrils, and restored cell viability, paving the way for preclinical translation of the approach.

中文翻译：

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载有富含多酚的葡萄渣提取物的脂质体在基于鱼藤酮的帕金森病体外模型中防止神经变性

帕金森病 (PD) 是一种进行性神经退行性疾病，没有令人满意的治疗选择。与其他神经退行性疾病（如阿尔茨海默病和亨廷顿病）类似，氧化应激在神经退行性疾病过程中起着关键作用。为了抵消活性氧 (ROS) 不受控制的增加和氧化应激依赖性细胞死亡，一些临床前和临床试验利用天然来源的有机抗氧化剂，如多酚。尽管取得了一些有希望的结果，但游离抗氧化剂显示出很少的大脑积累，并且可能在到达大脑之前耗尽它们的清除活动。在这项工作中，我们开发了一种抗氧化治疗纳米平台，该平台由纳米尺寸的功能化脂质体组成，其中装载有选定的富含多酚的植物提取物，具有高血脑屏障穿越能力。抗氧化提取物是从葡萄籽和葡萄皮中提取的，作为葡萄酒生产的副产品（即果渣），遵循可持续的循环方法，减少对环境的影响。该抗氧化剂纳米平台在相关的 PD体外模型中成功进行了测试，它完全挽救了 ROS 水平，防止了 α-突触核蛋白原纤维的聚集，并恢复了细胞活力，为该方法的临床前转化铺平了道路。