[HTML][HTML] Novel insights into the antioxidant role of tauroursodeoxycholic acid in experimental models of Parkinson's disease
AI Rosa, I Fonseca, MJ Nunes, S Moreira… - … et Biophysica Acta (BBA …, 2017 - Elsevier
Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 2017•Elsevier
Impaired mitochondrial function and generation of reactive oxygen species are deeply
implicated in Parkinson's disease progression. Indeed, mutations in genes that affect
mitochondrial function account for most of the familial cases of the disease, and post mortem
studies in sporadic PD patients brains revealed increased signs of oxidative stress.
Moreover, exposure to 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP), a
mitochondrial complex I inhibitor, leads to clinical symptoms similar to sporadic PD. The bile …
implicated in Parkinson's disease progression. Indeed, mutations in genes that affect
mitochondrial function account for most of the familial cases of the disease, and post mortem
studies in sporadic PD patients brains revealed increased signs of oxidative stress.
Moreover, exposure to 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP), a
mitochondrial complex I inhibitor, leads to clinical symptoms similar to sporadic PD. The bile …
Abstract
Impaired mitochondrial function and generation of reactive oxygen species are deeply implicated in Parkinson's disease progression. Indeed, mutations in genes that affect mitochondrial function account for most of the familial cases of the disease, and post mortem studies in sporadic PD patients brains revealed increased signs of oxidative stress. Moreover, exposure to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a mitochondrial complex I inhibitor, leads to clinical symptoms similar to sporadic PD.
The bile acid tauroursodeoxycholic acid (TUDCA) is an anti-apoptotic molecule shown to protect against MPTP-induced neurodegeneration in mice, but the mechanisms involved are still incompletely identified.
Herein we used MPTP-treated mice, as well as primary cultures of mice cortical neurons and SH-SY5Y cells treated with MPP+ to investigate the modulation of mitochondrial dysfunction by TUDCA in PD models. We show that TUDCA exerts its neuroprotective role in a parkin-dependent manner. Overall, our results point to the pharmacological up-regulation of mitochondrial turnover by TUDCA as a novel neuroprotective mechanism of this molecule, and contribute to the validation of TUDCA clinical application in PD.
Elsevier
