Department of Environmental Science, Baylor University, Waco, TX 76798, USA.
Int J Mol Sci. 2023 Nov 9;24(22):16129. doi: 10.3390/ijms242216129.
Parkinson's disease (PD) is a neurodegenerative condition marked by loss of motor coordination and cognitive impairment. According to global estimates, the worldwide prevalence of PD will likely exceed 12 million cases by 2040. PD is primarily associated with genetic factors, while clinically, cases are attributed to idiopathic factors such as environmental or occupational exposure. The heavy metals linked to PD and other neurodegenerative disorders include copper, manganese, and zinc. Chronic exposure to metals induces elevated oxidative stress and disrupts homeostasis, resulting in neuronal death. These metals are suggested to induce idiopathic PD in the literature. This study measures the effects of lethal concentration at 10% cell death (LC) and lethal concentration at 50% cell death (LC) concentrations of copper, manganese, and zinc chlorides on SH-SY5Y cells via markers for dopamine, reactive oxygen species (ROS) generation, DNA damage, and mitochondrial dysfunction after a 24 h exposure. These measurements were compared to a known neurotoxin to induce PD, 100 µM 6-hydroxydopamine (6-ODHA). Between the three metal chlorides, zinc was statistically different in all parameters from all other treatments and induced significant dopaminergic loss, DNA damage, and mitochondrial dysfunction. The LC of manganese and copper had the most similar response to 6-ODHA in all parameters, while LC of manganese and copper responded most like untreated cells. This study suggests that these metal chlorides respond differently from 6-ODHA and each other, suggesting that idiopathic PD utilizes a different mechanism from the classic PD model.
帕金森病（PD）是一种神经退行性疾病，其特征是运动协调丧失和认知障碍。根据全球估计，到 2040 年，全球 PD 患者人数可能超过 1200 万。PD 主要与遗传因素有关，而在临床上，病例归因于特发性因素，如环境或职业暴露。与 PD 和其他神经退行性疾病相关的重金属包括铜、锰和锌。慢性暴露于这些金属会引起氧化应激升高和体内平衡破坏，导致神经元死亡。文献中提示这些金属会导致特发性 PD。本研究通过测定多巴胺、活性氧（ROS）生成、DNA 损伤和线粒体功能障碍标志物，测量了氯化铜、氯化锰和氯化锌在 SH-SY5Y 细胞中的 10%细胞死亡致死浓度（LC）和 50%细胞死亡致死浓度（LC）对细胞的影响，暴露 24 小时后。将这些测量结果与已知的 PD 神经毒素 100µM 6-羟基多巴胺（6-ODHA）进行比较。在这三种金属氯化物中，锌在所有参数上与所有其他处理都有统计学差异，并导致多巴胺能显著丧失、DNA 损伤和线粒体功能障碍。锰和铜的 LC 在所有参数上与 6-ODHA 的反应最相似，而锰和铜的 LC 与未处理细胞的反应最相似。本研究表明，这些金属氯化物与 6-ODHA 及彼此之间的反应不同，提示特发性 PD 采用了不同于经典 PD 模型的机制。
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