Rosado-Ramos Rita, Godinho-Pereira Joana, Marques Daniela, Figueira Inês, Fleming Outeiro Tiago, Menezes Regina, Nunes Dos Santos Cláudia
iBET, Instituto de Biologia Experimental e Tecnológica, Av. da República, Apartado 12, 2781-901 Oeiras, Portugal.
Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República, 2780-157 Oeiras, Portugal.
Molecules. 2021 Jun 2;26(11):3353. doi: 10.3390/molecules26113353.
Phenolic compounds are thought to be important to prevent neurodegenerative diseases (ND). Parkinson's Disease (PD) is a neurodegenerative disorder known for its typical motor features, the deposition of α-synuclein (αsyn)-positive inclusions in the brain, and for concomitant cellular pathologies that include oxidative stress and neuroinflammation. Neuroprotective activity of fisetin, a dietary flavonoid, was evaluated against main hallmarks of PD in relevant cellular models. At physiologically relevant concentrations, fisetin protected SH-SY5Y cells against oxidative stress overtaken by -butyl hydroperoxide (-BHP) and against methyl-4-phenylpyridinuim (MPP)-induced toxicity in dopaminergic neurons, the differentiated Lund human Mesencephalic (LUHMES) cells. In this cellular model, fisetin promotes the increase of the levels of dopamine transporter. Remarkably, fisetin reduced the percentage of cells containing αsyn inclusions as well as their size and subcellular localization in a yeast model of αsyn aggregation. Overall, our data show that fisetin exerts modulatory activities toward common cellular pathologies present in PD; remarkably, it modulates αsyn aggregation, supporting the idea that diets rich in this compound may prove beneficial.
酚类化合物被认为对预防神经退行性疾病（ND）很重要。帕金森病（PD）是一种神经退行性疾病，以其典型的运动特征、大脑中α-突触核蛋白（αsyn）阳性包涵体的沉积以及包括氧化应激和神经炎症在内的伴随细胞病变为特征。在相关细胞模型中评估了膳食黄酮类化合物非瑟酮对PD主要特征的神经保护活性。在生理相关浓度下，非瑟酮保护SH-SY5Y细胞免受叔丁基过氧化氢（t-BHP）引起的氧化应激以及甲基-4-苯基吡啶鎓（MPP）对多巴胺能神经元（分化的隆德人脑中脑（LUHMES）细胞）诱导的毒性。在这个细胞模型中，非瑟酮促进多巴胺转运体水平的增加。值得注意的是，在αsyn聚集的酵母模型中，非瑟酮降低了含有αsyn包涵体的细胞百分比以及它们的大小和亚细胞定位。总体而言，我们的数据表明非瑟酮对PD中存在的常见细胞病变具有调节活性；值得注意的是，它调节αsyn聚集，支持富含这种化合物的饮食可能有益的观点。
