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 Deleidi; Rosamaria Silipigni; Monica Nizzardo; Nereo Bresolin; Giacomo P. Comi; Stefania Corti; Catarina M. Quinzii; Alessio Di Fonzo

doi:10.1016/j.stemcr.2018.09.007

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 journal › Article › peer-review

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 language	English
Pages (from-to)	1185-1198
Number of pages	14
Journal	Stem Cell Reports
Volume	11
Issue number	5
DOIs	https://doi.org/10.1016/j.stemcr.2018.09.007
Publication status	Published - 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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10.1016/j.stemcr.2018.09.007

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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

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, Deleidi, M, Silipigni, R, Nizzardo, M, Bresolin, N , Comi, GP , Corti, S, Quinzii, CM & Di Fonzo, A 2018, 'Mitochondrial Dysregulation and Impaired Autophagy in iPSC-Derived Dopaminergic Neurons of Multiple System Atrophy', Stem Cell Reports, vol. 11, no. 5, pp. 1185-1198. https://doi.org/10.1016/j.stemcr.2018.09.007

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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.",

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AU - Monzio Compagnoni, Giacomo

AU - Kleiner, Giulio

AU - Samarani, Maura

AU - Aureli, Massimo

AU - Faustini, Gaia

AU - Bellucci, Arianna

AU - Ronchi, Dario

AU - Bordoni, Andreina

AU - Garbellini, Manuela

AU - Salani, Sabrina

AU - Fortunato, Francesco

AU - Frattini, Emanuele

AU - Abati, Elena

AU - Bergamini, Christian

AU - Fato, Romana

AU - Tabano, Silvia

AU - Miozzo, Monica

AU - Serratto, Giulia

AU - Passafaro, Maria

AU - Deleidi, Michela

AU - Silipigni, Rosamaria

AU - Nizzardo, Monica

AU - Bresolin, Nereo

AU - Comi, Giacomo P.

AU - Corti, Stefania

AU - Quinzii, Catarina M.

AU - Di Fonzo, Alessio

PY - 2018/11/13

Y1 - 2018/11/13

N2 - 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.

AB - 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.

KW - autophagy

KW - dopaminergic neurons

KW - induced pluripotent stem cells

KW - mitochondria

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KW - multiple system atrophy

KW - neurodegeneration

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

Abstract

Keywords

ASJC Scopus subject areas

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