期刊
EXPERIMENTAL NEUROLOGY
卷 295, 期 -, 页码 77-87出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2017.05.009
关键词
TUDCA; MPTP/MPP; Nrf2; Oxidative stress; Redox balance; alpha-Synuclein
资金
- Fundacao para a Ciencia e a Tecnologia (FCT), Portugal [PTDC/NEU-NMC/0248/2012, UID/DTP/04138/2013, SFRH/BPD72891/2010, SFRH/BPD/95855/2013, SFRH/BPD/98023/2013]
- DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB)
- Fundação para a Ciência e a Tecnologia [PTDC/NEU-NMC/0248/2012, SFRH/BPD/98023/2013] Funding Source: FCT
Parkinson's disease (PD) is a progressive neurological disorder, mainly characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta. Although the cause of PD remains elusive, mitochondrial dysfunction and severe oxidative stress are strongly implicated in the cell death that characterizes the disease. Under oxidative stress, the master regulator of cellular redox status, nuclear factor erythroid 2 related factor 2 (Nrf2), is responsible for activating the transcription of several cytoprotective enzymes, namely glutathione peroxidase (GPx) and heme oxygenase-1 (HO-1). Nrf2 is a promising target to limit reactive oxygen species (ROS)-mediated damage in PD. Here, we show that tauroursodeoxycholic acid (TUDCA) prevents both 1-methyl-4-phenylpyridinium (MPP+)and a-synuclein-induced oxidative stress, through Nrf2 activation, in SH-SY5Y cells. Additionally, we used C57BL/6 male mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to elucidate the effect of TUDCA in this in vivo model of PD. In vivo, TUDCA treatment increases the expression of Nrf2, Nrf2 stabilizer DJ 1, and Nrf2 downstream target antioxidant enzymes HO-1 and GPx. Moreover, we found that TUDCA enhances GPx activity in the brain. Altogether, our results suggest that TUDCA is a promising agent to limit ROS-mediated damage, in different models of PD acting, at least in part, through modulation of the Nrf2 signaling pathway. Therefore, TUDCA should be considered a promising therapeutic agent to be implemented in PD. (C) 2017 Elsevier Inc. All rights reserved.
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