Novel insights into the antioxidant role of tauroursodeoxycholic acid in experimental models of Parkinson's disease

Alexandra I Rosa, Inês Fonseca, Maria João Nunes, Sara Moreira, Elsa Rodrigues, Andreia Neves Carvalho, Cecília M P Rodrigues, Maria João Gama, Margarida Castro-Caldas

Research output: Contribution to journalArticle

20 Citations (Scopus)

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 postmortem 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.

Original languageEnglish
Pages (from-to)2171-2181
JournalBiochimica Et Biophysica Acta
Volume1863
Issue number9
DOIs
Publication statusE-pub ahead of print - 2 Jun 2017

Keywords

  • TUDCA
  • Parkinson's disease
  • Oxidative stress
  • Mitochondria
  • Mitophagy
  • Parkin

Fingerprint Dive into the research topics of 'Novel insights into the antioxidant role of tauroursodeoxycholic acid in experimental models of Parkinson's disease'. Together they form a unique fingerprint.

  • Cite this