The detrimental impact on the food chain due to the overuse of rotenone is partly responsible for alpha-synuclein (α-syn) mediated neurotoxicity. It is hypothesized that rotenone overdose leads to cytosolic proteopathy resulting in modulation of apoptosis and autophagic pathways. The aim of our study is to explore the neuroprotective role of quercetin, a beneficial polyphenol against rotenone-induced neurotoxicity in dopaminergic human SH-SY5Y cell lines. In our study we demonstrated the correlation of rotenone-induced neurotoxicity through elevation of intracellular reactive oxygen species (ROS) and imbalance in the mitochondrial membrane potential (MMP). Moreover, the morphological distortion of cell, condensation of nuclei, externalization of the inner phosphatidylserine, cleavage of caspase 3, and Poly ADP Ribose Polymerase (PARP) confirmed apoptosis. However, all these lethal effects were ameliorated by treatment of quercetin to the cells. On the other hand rotenone has a strong effect on autophagy which is a regulated degrading and recycling cellular process to remove dysfunctional proteins. Indeed, rotenone-mediated autophagy resulted in the enhancement of autophagosome-bound microtubule-associated protein light chain-3 (LC3-II) expression. Furthermore, excess accumulation of acidic vesicles was detected in presence of rotenone. Lysosome associated membrane protein (LAMP-2A) is yet another crucial protein that recruits overexpressed or misfolded proteins into the lumen of lysosome to trigger autophagy. In all cases the impact of rotenone on the cells acquired significant protection through quercetin treatment. In the present work we therefore opine the prospects of quercetin as a therapeutic candidate against neurotoxicity.

鱼藤酮的过度使用对食物链的有害影响部分是由α-突触核蛋白（α-syn）介导的神经毒性造成的。假设鱼藤酮过量会导致胞质蛋白病，从而导致细胞凋亡和自噬途径的调节。我们研究的目的是探索槲皮素的神经保护作用，槲皮素是一种抗鱼藤酮诱导的人多巴胺能人SH-SY5Y细胞系神经毒性的有益多酚。在我们的研究中，我们证明了鱼藤酮诱导的神经毒性与细胞内活性氧（ROS）升高和线粒体膜电位（MMP）失衡有关。此外，细胞的形态变形，细胞核浓缩，内部磷脂酰丝氨酸的内在化，胱天蛋白酶3的裂解，和聚ADP核糖聚合酶（PARP）证实细胞凋亡。然而，通过槲皮素处理细胞可以改善所有这些致死作用。另一方面，鱼藤酮对自噬具有很强的作用，自噬是一种受控的降解和再循环细胞过程，以去除功能异常的蛋白质。确实，鱼藤酮介导的自噬导致自噬体结合的微管相关蛋白轻链3（LC3-II）表达的增强。此外，在鱼藤酮的存在下检测到酸性囊泡的过量积累。溶酶体相关膜蛋白（LAMP-2A）是又一个至关重要的蛋白，它将过量表达或错误折叠的蛋白募集到溶酶体腔中以触发自噬。在所有情况下，鱼藤酮都通过槲皮素处理对细胞产生明显的保护作用。