Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, Selangor Darul Ehsan, 47500, Bandar Sunway, Malaysia.
Department of Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia, 56000, Kuala Lumpur, Malaysia.
J Mol Neurosci. 2024 Sep 19;74(4):88. doi: 10.1007/s12031-024-02267-7.
Parkinson's disease (PD) is a common motor neurodegenerative disease that still lacks effective therapeutic options. Previous studies have reported that lactoferrin exhibited neuroprotective effects in cellular and animal models of PD, typically induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 1-methyl-4-phenylpyridinium (MPP) synthetic toxin. However, the neuroprotective capacity of lactoferrin in the rotenone-induced cellular model of PD remains relatively less established. Unlike MPTP/MPP, rotenone is a naturally occurring environmental toxin known to induce chronic toxicity and increase the risk of PD in humans. In this study, we constructed a cellular model of PD by differentiating SH-SY5Y neuroblastoma cells with retinoic acid into mature dopaminergic neurons with increased β-tubulin III and tyrosine hydroxylase expression, followed by 24 h of rotenone exposure. Using this cellular model of PD, we showed that lactoferrin (1-10 µg/ml) pre-treatment for 48 h decreased loss of cell viability, mitochondrial membrane potential impairment, reactive oxygen species generation and pro-apoptotic activities (pan-caspase activation and nuclear condensation) in cells exposed to rotenone (1 and 5 µM) using biochemical assays, Hoechst 33342 staining and immunocytochemical techniques. We further demonstrated that 48 h of lactoferrin (10 µg/ml) pre-treatment decreased Bax:Bcl2 ratio and p42/44 mitogen-activated protein kinase expression but increased pAkt expression in 5 µM rotenone-exposed cells. Our study demonstrates that lactoferrin neuroprotective capacity is present in the rotenone-induced cellular model of PD, further supporting lactoferrin as a potential PD therapeutic that warrants further studies.
帕金森病（PD）是一种常见的运动神经退行性疾病，目前仍然缺乏有效的治疗选择。先前的研究报告称，乳铁蛋白在 PD 的细胞和动物模型中表现出神经保护作用，这些模型通常是由 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）或 1-甲基-4-苯基吡啶（MPP）合成毒素诱导的。然而，乳铁蛋白在鱼藤酮诱导的 PD 细胞模型中的神经保护能力相对较少得到证实。与 MPTP/MPP 不同，鱼藤酮是一种天然存在的环境毒素，已知会导致慢性毒性，并增加人类患 PD 的风险。在这项研究中，我们通过用视黄酸将 SH-SY5Y 神经母细胞瘤细胞分化为成熟的多巴胺能神经元，并增加 β-微管蛋白 III 和酪氨酸羟化酶的表达，然后用鱼藤酮暴露 24 小时来构建 PD 的细胞模型。使用这种 PD 细胞模型，我们表明乳铁蛋白（1-10 µg/ml）预处理 48 小时可降低暴露于鱼藤酮（1 和 5 µM）的细胞中的细胞活力丧失、线粒体膜电位损伤、活性氧生成和促凋亡活性（全胱天冬酶激活和核浓缩），通过生化测定、Hoechst 33342 染色和免疫细胞化学技术。我们进一步表明，乳铁蛋白（10 µg/ml）预处理 48 小时可降低 Bax：Bcl2 比值和 p42/44 丝裂原活化蛋白激酶的表达，但增加 5 µM 鱼藤酮暴露细胞中 pAkt 的表达。我们的研究表明，乳铁蛋白的神经保护能力存在于鱼藤酮诱导的 PD 细胞模型中，进一步支持乳铁蛋白作为一种有潜力的 PD 治疗药物，值得进一步研究。
