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α-硫辛酸通过调节6-羟基多巴胺诱导的帕金森病模型中的铁代谢来介导铁蓄积的清除。

Alpha-Lipoic Acid Mediates Clearance of Iron Accumulation by Regulating Iron Metabolism in a Parkinson's Disease Model Induced by 6-OHDA.

作者信息

Tai Shengyan, Zheng Qian, Zhai Suzhen, Cai Ting, Xu Li, Yang Lizhu, Jiao Ling, Zhang Chunlin

机构信息

Department of Biology, College of Basic Medical, Guizhou Medical University, Guiyang, China.

Department of Neurology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China.

出版信息

Front Neurosci. 2020 Jun 25;14:612. doi: 10.3389/fnins.2020.00612. eCollection 2020.

Abstract

The disruption of neuronal iron homeostasis and oxidative stress are related to the pathogenesis of Parkinson's disease (PD). Alpha-lipoic acid (ALA) is a naturally occurring enzyme cofactor with antioxidant and iron chelator properties and has many known effects. ALA has neuroprotective effects on PD. However, its underlying mechanism remains unclear. In the present study, we established PD models induced by 6-hydroxydopamine (6-OHDA) to explore the neuroprotective ability of ALA and its underlying mechanism and . Our results showed that ALA could provide significant protection from 6-OHDA-induced cell damage by decreasing the levels of intracellular reactive oxygen species and iron. ALA significantly promoted the survival of the dopaminergic neuron in the 6-OHDA-induced PD rat model and remarkably ameliorated motor deficits by dramatically inhibiting the decrease in tyrosine hydroxylase expression and superoxide dismutase activity in the substantia nigra. Interestingly, ALA attenuated 6-OHDA-induced iron accumulation both and by antagonizing the 6-OHDA-induced upregulation of iron regulatory protein 2 and divalent metal transporter 1. These results indicated that the neuroprotective mechanism of ALA against neurological injury induced by 6-OHDA may be related to the regulation of iron homeostasis and reduced oxidative stress levels. Therefore, ALA may provide neuroprotective therapy for PD and other diseases related to iron metabolism disorder.

摘要

神经元铁稳态的破坏和氧化应激与帕金森病(PD)的发病机制有关。α-硫辛酸(ALA)是一种天然存在的具有抗氧化和铁螯合特性的酶辅因子,具有多种已知作用。ALA对PD具有神经保护作用。然而,其潜在机制仍不清楚。在本研究中,我们建立了由6-羟基多巴胺(6-OHDA)诱导的PD模型,以探讨ALA的神经保护能力及其潜在机制。我们的结果表明,ALA可通过降低细胞内活性氧和铁的水平,为6-OHDA诱导的细胞损伤提供显著保护。在6-OHDA诱导的PD大鼠模型中,ALA显著促进多巴胺能神经元的存活,并通过显著抑制黑质中酪氨酸羟化酶表达和超氧化物歧化酶活性的降低,明显改善运动功能障碍。有趣的是,ALA通过拮抗6-OHDA诱导的铁调节蛋白2和二价金属转运体1的上调,减轻了6-OHDA诱导的铁积累。这些结果表明,ALA对6-OHDA诱导的神经损伤的神经保护机制可能与铁稳态的调节和氧化应激水平的降低有关。因此,ALA可能为PD和其他与铁代谢紊乱相关的疾病提供神经保护治疗。

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