Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung 40201, Taiwan.
Department of Nutrition, China Medical University, Taichung 40402, Taiwan.
Int J Mol Sci. 2020 Jun 23;21(12):4455. doi: 10.3390/ijms21124455.
The movement disorder Parkinson's disease (PD) is the second most frequently diagnosed neurodegenerative disease, and is associated with aging, the environment, and genetic factors. The intracellular aggregation of α-synuclein and the loss of dopaminergic neurons in the substantia nigra pars compacta are the pathological hallmark of PD. At present, there is no successful treatment for PD. Maackiain (MK) is a flavonoid extracted from dried roots of Aiton. MK has emerged as a novel agent for PD treatment that acts by inhibiting monoamine oxidase B. In this study, we assessed the neuroprotective potential of MK in and investigated possible mechanism of this neuroprotection in the human SH-SY5Y cell line. We found that MK significantly reduced dopaminergic neuron damage in 6-hydroxydopamine (6-OHDA)-exposed worms of the BZ555 strain, with corresponding improvements in food-sensing behavior and life-span. In transgenic worms of strain NL5901 treated with 0.25 mM MK, the accumulation of α-synuclein was diminished by 27% ( < 0.01) compared with that in untreated worms. Moreover, in worms and the SH-SY5Y cell line, we confirmed that the mechanism of MK-mediated protection against PD pathology may include blocking apoptosis, enhancing the ubiquitin-proteasome system, and augmenting autophagy by increasing expression. The use of small interfering RNA to downregulate parkin expression in vivo and in vitro could reverse the benefits of MK in PD models. MK may have considerable therapeutic applications in PD.
运动障碍性疾病帕金森病（PD）是第二大常见的神经退行性疾病，与衰老、环境和遗传因素有关。α-突触核蛋白的细胞内聚集和黑质致密部多巴胺能神经元的丧失是 PD 的病理标志。目前，PD 尚无成功的治疗方法。马卡因（MK）是从 Aiton 干根中提取的一种黄酮类化合物。MK 作为一种新型 PD 治疗药物，通过抑制单胺氧化酶 B 发挥作用。在本研究中，我们评估了 MK 在 中的神经保护潜力，并在人 SH-SY5Y 细胞系中研究了这种神经保护的可能机制。我们发现 MK 可显著减轻 6-羟多巴胺（6-OHDA）暴露的 BZ555 品系蠕虫中多巴胺能神经元的损伤，并相应改善其食物感知行为和寿命。在 NL5901 品系的转基因蠕虫中，用 0.25mM MK 处理后，α-突触核蛋白的积累减少了 27%（ < 0.01），与未处理的蠕虫相比。此外，在蠕虫和 SH-SY5Y 细胞系中，我们证实 MK 介导的 PD 病理保护机制可能包括阻断细胞凋亡、增强泛素-蛋白酶体系统以及通过增加 表达增强自噬。体内和体外使用小干扰 RNA 下调 parkin 表达可以逆转 MK 在 PD 模型中的益处。MK 可能在 PD 中有相当大的治疗应用。
