State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guizhou, 550004, China.
Engineering Technology Research Center for Chemical Drug R&D, Guizhou, 550004, China.
Neurotox Res. 2018 May;33(4):759-767. doi: 10.1007/s12640-017-9819-5. Epub 2017 Oct 10.
The precise mechanisms underlying neuronal injury in Parkinson's disease (PD) are not yet fully elucidated; however, evidence from the in vitro and in vivo PD models suggest that mitochondrial dysfunction may play a major role in PD pathogenesis. Alpha lipoamide, a neutral amide derivative of the lipoic acid, is a better cofactor for mitochondrial dehydrogenase with a stronger protective effect on mitochondria than lipoic acid. Identification of these protective effects of alpha lipoamide on mitochondria, together with the evidence that mitochondrial dysfunction plays a critical role in PD, we speculate that alpha lipoamide may exert a protective effect in PD by regulating the mitochondrial function. The present study investigated the neuroprotective effects of alpha lipoamide in an animal model of PD induced by 6-hydroxydopamine (6-OHDA). The results demonstrated that alpha lipoamide could significantly antagonize the 6-OHDA-induced behavioral damages; restore ATP levels in the midbrain; and also improve the fragmentation, vacuolization, and morphology of the mitochondria. The results of Western blot indicated that alpha lipoamide significantly restored the number of dopaminergic neurons in midbrain and substantially recovered the balance between mitochondrial fission, fusion, and transport. In conclusion, the results demonstrated that alpha lipoamide might exert a significant neuroprotective effect in the animal model of PD by regulation of the dynamic properties of mitochondria.
帕金森病(PD)中神经元损伤的确切机制尚未完全阐明;然而,来自 PD 体外和体内模型的证据表明,线粒体功能障碍可能在 PD 发病机制中起主要作用。α-硫辛酸是硫辛酸的中性酰胺衍生物,是线粒体脱氢酶的更好辅助因子,对线粒体的保护作用比硫辛酸更强。鉴定α-硫辛酸对线粒体的这些保护作用,以及线粒体功能障碍在 PD 中起关键作用的证据,我们推测α-硫辛酸可能通过调节线粒体功能在 PD 中发挥保护作用。本研究探讨了α-硫辛酸在 6-羟多巴胺(6-OHDA)诱导的 PD 动物模型中的神经保护作用。结果表明,α-硫辛酸能显著拮抗 6-OHDA 引起的行为损伤;恢复中脑 ATP 水平;并改善线粒体的碎片化、空泡化和形态。Western blot 结果表明,α-硫辛酸可显著恢复中脑多巴胺能神经元的数量,并显著恢复线粒体分裂、融合和运输之间的平衡。总之,结果表明,α-硫辛酸可能通过调节线粒体的动态特性在 PD 动物模型中发挥显著的神经保护作用。