iBET, Instituto de Biologia Experimental e Tecnológica, Oeiras, Portugal.
Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa (ITQB NOVA), Oeiras, Portugal.
Nat Commun. 2023 Apr 6;14(1):1918. doi: 10.1038/s41467-023-37561-2.
Parkinson's Disease (PD) is a common neurodegenerative disorder affecting millions of people worldwide for which there are only symptomatic therapies. Small molecules able to target key pathological processes in PD have emerged as interesting options for modifying disease progression. We have previously shown that a (poly)phenol-enriched fraction (PEF) of Corema album L. leaf extract modulates central events in PD pathogenesis, namely α-synuclein (αSyn) toxicity, aggregation and clearance. PEF was now subjected to a bio-guided fractionation with the aim of identifying the critical bioactive compound. We identified genipin, an iridoid, which relieves αSyn toxicity and aggregation. Furthermore, genipin promotes metabolic alterations and modulates lipid storage and endocytosis. Importantly, genipin was able to prevent the motor deficits caused by the overexpression of αSyn in a Drosophila melanogaster model of PD. These findings widens the possibility for the exploitation of genipin for PD therapeutics.
帕金森病（PD）是一种常见的神经退行性疾病，全球有数百万患者，目前只有对症治疗方法。能够针对 PD 关键病理过程的小分子已成为改变疾病进展的有趣选择。我们之前已经表明，Corema album L. 叶提取物的（多）酚丰富部分（PEF）调节 PD 发病机制中的中枢事件，即α-突触核蛋白（αSyn）毒性、聚集和清除。现在对 PEF 进行了生物导向的分级分离，以鉴定关键的生物活性化合物。我们鉴定出了京尼平，一种环烯醚萜，它可以缓解 αSyn 毒性和聚集。此外，京尼平还能促进代谢改变，并调节脂质储存和内吞作用。重要的是，京尼平能够预防由αSyn 在 PD 的黑腹果蝇模型中的过表达引起的运动缺陷。这些发现拓宽了京尼平在 PD 治疗中的应用可能性。
