Mitochondrial Dysregulation and Impaired Autophagy in iPSC-Derived Dopaminergic Neurons of Multiple System Atrophy

Giacomo Monzio Compagnoni, Giulio Kleiner, Maura Samarani, Massimo Aureli, Gaia Faustini, Arianna Bellucci, Dario Ronchi, Andreina Bordoni, Manuela Garbellini, Sabrina Salani, Francesco Fortunato, Emanuele Frattini, Elena Abati, Christian Bergamini, Romana Fato, Silvia Tabano, Monica Miozzo, Giulia Serratto, Maria Passafaro, Michela DeleidiRosamaria Silipigni, Monica Nizzardo, Nereo Bresolin, Giacomo P. Comi, Stefania Corti, Catarina M. Quinzii, Alessio Di Fonzo

Research output: Contribution to journalArticle

Abstract

Multiple system atrophy (MSA) is a progressive neurodegenerative disease that affects several areas of the CNS, whose pathogenesis is still widely unclear and for which an effective treatment is lacking. We have generated induced pluripotent stem cell-derived dopaminergic neurons from four MSA patients and four healthy controls and from two monozygotic twins discordant for the disease. In this model, we have demonstrated an aberrant autophagic flow and a mitochondrial dysregulation involving respiratory chain activity, mitochondrial content, and CoQ10 biosynthesis. These defective mechanisms may contribute to the onset of the disease, representing potential therapeutic targets.

Original languageEnglish
Pages (from-to)1185-1198
Number of pages14
JournalStem Cell Reports
Volume11
Issue number5
DOIs
Publication statusPublished - Nov 13 2018

Keywords

  • autophagy
  • dopaminergic neurons
  • induced pluripotent stem cells
  • mitochondria
  • MSA
  • multiple system atrophy
  • neurodegeneration

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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  • Cite this

    Monzio Compagnoni, G., Kleiner, G., Samarani, M., Aureli, M., Faustini, G., Bellucci, A., Ronchi, D., Bordoni, A., Garbellini, M., Salani, S., Fortunato, F., Frattini, E., Abati, E., Bergamini, C., Fato, R., Tabano, S., Miozzo, M., Serratto, G., Passafaro, M., ... Di Fonzo, A. (2018). Mitochondrial Dysregulation and Impaired Autophagy in iPSC-Derived Dopaminergic Neurons of Multiple System Atrophy. Stem Cell Reports, 11(5), 1185-1198. https://doi.org/10.1016/j.stemcr.2018.09.007