Vestuto Vincenzo, Amodio Giuseppina, Pepe Giacomo, Basilicata Manuela Giovanna, Belvedere Raffaella, Napolitano Enza, Guarnieri Daniela, Pagliara Valentina, Paladino Simona, Rodriquez Manuela, Bertamino Alessia, Campiglia Pietro, Remondelli Paolo, Moltedo Ornella
Department of Pharmacy, University of Salerno, I-84034 Fisciano-Salerno, Italy.
Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, I-84034 Baronissi-Salerno, Italy.
Biomedicines. 2022 Aug 18;10(8):2009. doi: 10.3390/biomedicines10082009.
Parkinson's disease (PD) represents one of the most common neurodegenerative disorders, characterized by a dopamine (DA) deficiency in striatal synapses and misfolded toxic α-synuclein aggregates with concomitant cytotoxicity. In this regard, the misfolded proteins accumulation in neurodegenerative disorders induces a remarkable perturbations of endoplasmic reticulum (ER) homeostasis leading to persistent ER stress, which in turn, effects protein synthesis, modification, and folding quality control. A large body of evidence suggests that natural products target the ER stress signaling pathway, exerting a potential action in cancers, diabetes, cardiovascular and neurodegenerative diseases. This study aims to assess the neuroprotective effect of cocoa extract and its purified fractions against a cellular model of Parkinson's disease represented by 6-hydroxydopamine (6-OHDA)-induced SH-SY5Y human neuroblastoma. Our findings demonstrate, for the first time, the ability of cocoa to specifically targets PERK sensor, with significant antioxidant and antiapoptotic activities as both crude and fractioning extracts. In addition, cocoa also showed antiapoptotic properties in 3D cell model and a notable ability to inhibit the accumulation of α-synuclein in 6-OHDA-induced cells. Overall, these results indicate that cocoa exerts neuroprotective effects suggesting a novel possible strategy to prevent or, at least, mitigate neurodegenerative disorders, such as PD.
帕金森病（PD）是最常见的神经退行性疾病之一，其特征是纹状体突触中多巴胺（DA）缺乏以及错误折叠的有毒α-突触核蛋白聚集体并伴有细胞毒性。在这方面，神经退行性疾病中错误折叠蛋白的积累会引起内质网（ER）稳态的显著紊乱，导致持续性内质网应激，进而影响蛋白质合成、修饰和折叠质量控制。大量证据表明，天然产物靶向内质网应激信号通路，在癌症、糖尿病、心血管疾病和神经退行性疾病中发挥潜在作用。本研究旨在评估可可提取物及其纯化组分对以6-羟基多巴胺（6-OHDA）诱导的SH-SY5Y人神经母细胞瘤为代表的帕金森病细胞模型的神经保护作用。我们的研究结果首次证明，可可能够特异性靶向PERK传感器，其粗提物和分级提取物均具有显著的抗氧化和抗凋亡活性。此外，可可在三维细胞模型中也显示出抗凋亡特性，并且在6-OHDA诱导的细胞中具有显著的抑制α-突触核蛋白积累的能力。总体而言，这些结果表明可可具有神经保护作用，提示了一种预防或至少减轻神经退行性疾病（如帕金森病）的新的可能策略。
