α-lipoic acid protects dopaminergic neurons against MPP+-induced apoptosis by attenuating reactive oxygen species formation

Li,Da-Wei; Li,Guang-Ren; Lu,Yan; Liu,Zhi-Qiang; Chang,Ming; Yao,Ming; Cheng,Wei; Hu,Lin-Sen

doi:10.3892/ijmm.2013.1361

α-lipoic acid protects dopaminergic neurons against MPP+-induced apoptosis by attenuating reactive oxygen species formation

Authors:
- Da-Wei Li
- Guang-Ren Li
- Yan Lu
- Zhi-Qiang Liu
- Ming Chang
- Ming Yao
- Wei Cheng
- Lin-Sen Hu
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Affiliations: Department of Neurology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of Neurology, The Third Hospital of Jilin University, Changchun, Jilin 130031, P.R. China
Published online on: April 24, 2013 https://doi.org/10.3892/ijmm.2013.1361
Pages: 108-114

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Abstract

Reactive oxygen species (ROS) elicited by oxidative stress are widely recognized as a major initiator in the degeneration of dopaminergic neurons distinctive of Parkinson's disease (PD). The interaction of ROS with mitochondria triggers sequential events in the mitochondrial cell death pathway, which is thought to be responsible for ROS-mediated neurodegeneration in PD. α-lipoic acid (LA) is a pleiotropic compound with potential pharmacotherapeutic value against a range of pathophysiological insults. Its protective actions against oxidative damage by scavenging ROS and reducing production of free radicals have been reported in various in vitro and in vivo systems. This study analyzed the ability of LA to protect PC12 neuronal cells from toxicity of 1-methyl-4-phenylpyridinium (MPP+), the neurotoxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) which is known to kill dopaminergic neurons selectively and to cause severe parkinsonism-like symptoms in humans and primate animals. Our results demonstrate that the apoptosis of PC12 cells elicited by MPP+ could be significantly prevented by pretreatment with LA for 1 h. In addition, LA inhibits intercellular ROS levels and the mitochondrial transmembrane permeability, the key players in the pathogenesis of PD, thereby protecting dopaminergic neuronal cells against oxidative damage.

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