The pathogenesis linked to coenzyme Q10 insufficiency in iPSC-derived neurons from patients with multiple-system atrophy

Scientific Reports
Fumiko Kusunoki NakamotoHideyuki Okano

Abstract

Multiple-system atrophy (MSA) is a neurodegenerative disease characterized by autonomic failure with various combinations of parkinsonism, cerebellar ataxia, and pyramidal dysfunction. We previously reported that functionally impaired variants of COQ2, which encodes an essential enzyme in the biosynthetic pathway of coenzyme Q10, are associated with MSA. Here, we report functional deficiencies in mitochondrial respiration and the antioxidative system in induced pluripotent stem cell (iPSC)-derived neurons from an MSA patient with compound heterozygous COQ2 mutations. The functional deficiencies were rescued by site-specific CRISPR/Cas9-mediated gene corrections. We also report an increase in apoptosis of iPSC-derived neurons from MSA patients. Coenzyme Q10 reduced apoptosis of neurons from the MSA patient with compound heterozygous COQ2 mutations. Our results reveal that cellular dysfunctions attributable to decreased coenzyme Q10 levels are related to neuronal death in MSA, particularly in patients with COQ2 variants, and may contribute to the development of therapy using coenzyme Q10 supplementation.

References

Oct 1, 1990·Journal of Nutritional Science and Vitaminology·Y YamamotoE Niki
Jun 1, 2000·Journal of the Neurological Sciences·T YamashitaM Uchino
Apr 19, 2002·Brain : a Journal of Neurology·Hirohisa WatanabeGen Sobue
May 18, 2004·Journal of Neurology, Neurosurgery, and Psychiatry·U WüllnerT Klockgether
Sep 15, 2005·Movement Disorders : Official Journal of the Movement Disorder Society·Felix GeserUNKNOWN European MSA Study Group
Nov 26, 2005·Journal of the Neurological Sciences·Hiroyuki SomaHidenao Sasaki
Jul 11, 2006·Journal of the Neurological Sciences·Ichiro YabeHidenao Sasaki
Apr 11, 2007·Archives of Neurology·Kenju HaraShoji Tsuji
Nov 17, 2009·Lancet Neurology·Nadia StefanovaGregor Karl Wenning
Jan 6, 2011·Proceedings of the National Academy of Sciences of the United States of America·Kosuke YusaNancy L Craig
Aug 5, 2011·Methods in Molecular Biology·Stephanie L H ZeigerBethAnn McLaughlin
Jun 14, 2013·The New England Journal of Medicine·UNKNOWN Multiple-System Atrophy Research Collaboration
Jul 6, 2014·The New England Journal of Medicine·Catarina M QuinziiSalvatore DiMauro
Nov 7, 2014·Molecular Neurodegeneration·Kotaro OgakiOwen A Ross
Dec 3, 2014·Neurobiology of Aging·Yong Ping ChenHui-Fang Shang
Jan 17, 2015·Movement Disorders : Official Journal of the Movement Disorder Society·Chin-Hsien LinRuey-Meei Wu
Nov 22, 2015·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·P S RommerUNKNOWN GRAID investigators
Nov 23, 2015·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·QuanZhen ZhaoYanming Xu
Feb 20, 2016·PloS One·Lucia V SchottlaenderHenry Houlden
May 29, 2016·Journal of Neuropathology and Experimental Neurology·Emanuele BarcaCatarina M Quinzii
Jul 1, 2016·JAMA Neurology·Jun MitsuiShoji Tsuji
Oct 22, 2016·Neurology·Anna SailerUNKNOWN European Multiple System Atrophy Study Group and the UK Multiple System Atrophy Study Group
Jun 15, 2017·Biochemical and Biophysical Research Communications·Misako MatsushitaMinoru S H Ko
Nov 7, 2017·Parkinsonism & Related Disorders·Yaroslau ComptaUNKNOWN Catalan MSA Registry (CMSAR)

❮ Previous
Next ❯

Citations

Jun 13, 2019·Clinical Autonomic Research : Official Journal of the Clinical Autonomic Research Society·Alain NdayisabaNadia Stefanova
Jul 14, 2019·Acta Neuropathologica Communications·Giacomo Monzio Compagnoni, Alessio Di Fonzo
Nov 27, 2019·World Journal of Stem Cells·Maria Teresa ValentiDonato Zipeto
Apr 23, 2020·International Journal of Molecular Sciences·Lisa MészárosJürgen Winkler
May 24, 2020·Molecular Neurobiology·Giacomo Monzio CompagnoniEliezer Masliah
Sep 7, 2020·Neuropathology and Applied Neurobiology·M Herrera-VaqueroN Stefanova
Jan 16, 2021·Free Radical Biology & Medicine·Naig GueguenMarco Spinazzi
Oct 30, 2020·International Journal of Molecular Sciences·Francisco Miguel Gutierrez-MariscalJose López-Miranda
May 1, 2021·International Journal of Molecular Sciences·Manami DeshimaruYoshio Tsuboi
May 6, 2021·Journal of Personalized Medicine·Wanda LattanziOrnella Parolini
Jul 29, 2021·Journal of Neural Transmission·Nicole CampeseGregor K Wenning
Jul 25, 2021·International Journal of Molecular Sciences·Cameron L McKnightAnn E Frazier
Aug 30, 2021·Journal of the Neurological Sciences·Kristine Joyce PortoShoji Tsuji
Oct 7, 2021·Journal of Neural Transmission·David J MarmionJeffrey H Kordower

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
transfection

Software Mentioned

IN Cell Analyzer
CellROX

Related Concepts

Related Feeds

Ataxia telangiectasia (MDS)

Ataxia telangiectasia is a rare neurodegenerative diseases caused by defects in the ATM gene, which is involved in DNA damage recognition and repair pathways. Here is the latest research on this autosomal recessive disease.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

CRISPR (general)

Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). CRISPR-Cas system enables the editing of genes to create or correct mutations. Discover the latest research on CRISPR here.

CRISPR for Genome Editing

Genome editing technologies enable the editing of genes to create or correct mutations. Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). Here is the latest research on the use of CRISPR-Cas system in gene editing.

CRISPR Ribonucleases Deactivation

CRISPR-Cas system enables the editing of genes to create or correct mutations. This feed focuses on mechanisms that underlie deactivation of CRISPR ribonucleases. Here is the latest research.

Ataxias

Ataxia is a neurological condition characterized by lack of voluntary coordination of muscle movements including loss of coordination, balance, and speech. Discover the latest research on different types of ataxias here.

© 2022 Meta ULC. All rights reserved