Overexpression of thioredoxin reductase 1 can reduce DNA damage, mitochondrial autophagy and endoplasmic reticulum stress in Parkinson's disease

被引:0
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作者
Zihua Liu
Qiang Ye
Fang Wang
Yanan Guo
Rong Cui
Jianlin Wang
Degui Wang
机构
[1] Lanzhou University,Department of Zoology and Biomedical Science, School of Life Sciences, Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution
[2] Lanzhou University,Department of Anatomy and Histology, School of Basic Medical Sciences
[3] Gynecology With Integrated Traditional Chinese and Western Medicine of Gansu Provincial Maternity and Child Care Hospital,Blood Transfusion Service
[4] The Second Affiliated Hospital of Lanzhou University,undefined
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关键词
Thioredoxin reductase 1; Parkinson's disease; ROS; DNA damage;
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摘要
Parkinson's disease (PD) is a neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra (SN). Several factors, including neuroinflammation, neuronal excitotoxicity, genetic mutations and incorrect protein folding are involved in PD pathophysiology. However, the precise mechanism that contributes to the decreased number of dopaminergic neurons is unknown. A growing body of research suggests that oxidative stress is a major factor in PD. Therefore, antioxidant therapy is an important approach for treating PD. The thioredoxin system is an important antioxidant system, and thioredoxin reductase 1 (TR1) is a major member of the thioredoxin system. The present study demonstrates that oxidative stress is increased and that the expression of TR1 is decreased in the SNc of A53T mice; TR1 has emerged as an important antioxidant agent in dopaminergic neurons. Therefore, we over-expressed TR1 in the MPP+-induced cellular model and in the A53T transgenic mouse model of PD. We confirmed that the overexpression of TR1 in neuronal cells decreased DNA damage and malondialdehyde (MDA) and ROS generation, increased T-SOD and GSH production, and decreased the ER stress, and autophagy in the PD model. In summary, our findings demonstrate that the overexpression of TR1 could be effective as a novel neuroprotective strategy for PD. This research suggests a novel direction in the treatment of PD.
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页码:475 / 490
页数:15
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