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

被引：45

作者：

Compagnoni, Giacomo Monzio ^{[1
]}

Kleiner, Giulio ^{[2
]}

Samarani, Maura ^{[3
]}

Aureli, Massimo ^{[3
]}

Faustini, Gaia ^{[4
]}

Bellucci, Arianna ^{[4
]}

Ronchi, Dario ^{[1
]}

Bordoni, Andreina ^{[1
]}

Garbellini, Manuela ^{[1
]}

Salani, Sabrina ^{[1
]}

Fortunato, Francesco ^{[1
]}

Frattini, Emanuele ^{[1
]}

Abati, Elena ^{[1
]}

Bergamini, Christian ^{[5
]}

Fato, Romana ^{[5
]}

Tabano, Silvia ^{[6
,10
]}

Miozzo, Monica ^{[6
,10
]}

Serratto, Giulia ^{[7
]}

Passafaro, Maria ^{[7
]}

Deleidi, Michela ^{[8
]}

Silipigni, Rosamaria ^{[9
]}

Nizzardo, Monica ^{[1
]}

Bresolin, Nereo ^{[1
]}

Comi, Giacomo P. ^{[1
]}

Corti, Stefania ^{[1
]}

Quinzii, Catarina M. ^{[2
]}

Di Fonzo, Alessio ^{[1
]}

机构：

[1] Univ Milan, Dept Pathophysiol & Transplantat, Dino Ferrari Ctr, IRCCS Fdn Ca Granda Osped Maggiore Policlin,Neuro, I-20122 Milan, Italy

[2] Columbia Univ, Dept Neurol, New York, NY 10032 USA

[3] Univ Milan, Dept Med Biotechnol & Translat Med, I-20090 Milan, Italy

[4] Univ Brescia, Dept Mol & Translat Med, I-25123 Brescia, Italy

[5] Univ Bologna, Dept Pharm & Biotechnol FaBiT, I-40126 Bologna, Italy

[6] Univ Milan, Dept Pathophysiol & Transplantat, I-20129 Milan, Italy

[7] Univ Milan, Dept Biometra, CNR, Inst Neurosci, I-20129 Milan, Italy

[8] Univ Tubingen, Hertie Inst Clin Brain Res, German Ctr Neurodegenerat Dis DZNE, Otfried Muller Str 23, D-72076 Tubingen, Germany

[9] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Lab Med Genet, I-20122 Milan, Italy

[10] Osped Maggiore Policlin, IRCCS Ca Granda, Div Pathol, I-20122 Milan, Italy

来源：

STEM CELL REPORTS | 2018年 / 11卷 / 05期

关键词：

ALPHA-SYNUCLEIN EXPRESSION; MOUSE MODEL; CELLS;

D O I：

10.1016/j.stemcr.2018.09.007

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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.

引用

页码：1185 / 1198

页数：14

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