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Molecular Neurobiology

, Volume 54, Issue 8, pp 6107–6119 | Cite as

Tauroursodeoxycholic Acid Protects Against Mitochondrial Dysfunction and Cell Death via Mitophagy in Human Neuroblastoma Cells

  • Inês Fonseca
  • Gisela Gordino
  • Sara Moreira
  • Maria João Nunes
  • Carla Azevedo
  • Maria João Gama
  • Elsa Rodrigues
  • Cecília Maria Pereira Rodrigues
  • Margarida Castro-CaldasEmail author
Article

Abstract

Mitochondrial dysfunction has been deeply implicated in the pathogenesis of several neurodegenerative diseases. Thus, to keep a healthy mitochondrial population, a balanced mitochondrial turnover must be achieved. Tauroursodeoxycholic acid (TUDCA) is neuroprotective in various neurodegenerative disease models; however, the mechanisms involved are still incompletely characterized. In this study, we investigated the neuroprotective role of TUDCA against mitochondrial damage triggered by the mitochondrial uncoupler carbonyl cyanide m-chlorophelyhydrazone (CCCP). Herein, we show that TUDCA significantly prevents CCCP-induced cell death, ROS generation, and mitochondrial damage. Our results indicate that the neuroprotective role of TUDCA in this cell model is mediated by parkin and depends on mitophagy. The demonstration that pharmacological up-regulation of mitophagy by TUDCA prevents neurodegeneration provides new insights for the use of TUDCA as a modulator of mitochondrial activity and turnover, with implications in neurodegenerative diseases.

Keywords

TUDCA Mitochondria Autophagy Mitophagy Parkin SH-SY5Y cells 

Notes

Acknowledgments

This work was supported by research grants UID/DTP/04138/2013 (iMed.ULisboa), PTDC/NEU-NMC/0248/2012 (to M.C.C.), fellowship in project PTDC/NEU-OSD/0502/2012 (to C.A.) and post-doctoral fellowship SFRH/BPD/95855/2013 (to M.J.N.) from Fundação para a Ciência e a Tecnologia (FCT), Portugal.

Supplementary material

12035_2016_145_MOESM1_ESM.docx (5.6 mb)
ESM 1 (DOCX 5706 kb)

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Inês Fonseca
    • 1
  • Gisela Gordino
    • 1
  • Sara Moreira
    • 1
  • Maria João Nunes
    • 1
  • Carla Azevedo
    • 1
  • Maria João Gama
    • 1
    • 2
  • Elsa Rodrigues
    • 1
    • 2
  • Cecília Maria Pereira Rodrigues
    • 1
    • 2
  • Margarida Castro-Caldas
    • 1
    • 3
    Email author
  1. 1.Research Institute for Medicines (iMed.ULisboa), Faculty of PharmacyUniversidade de LisboaLisbonPortugal
  2. 2.Department of Biochemistry and Human Biology, Faculty of PharmacyUniversidade de LisboaLisbonPortugal
  3. 3.Department of Life Sciences, Faculty of Science and TechnologyUniversidade NOVA de LisboaCaparicaPortugal

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