Nrf2 activation by tauroursodeoxycholic acid in experimental models of Parkinson's disease.

Nrf2 activation by tauroursodeoxycholic acid in experimental models of Parkinson's disease. Exp Neurol. 2017 May 25;: Authors: Moreira S, Fonseca I, Nunes MJ, Rosa A, Lemos L, Rodrigues E, Carvalho AN, Outeiro TF, Rodrigues CMP, Gama MJ, Castro-Caldas M Abstract 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 α-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. Mo...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research