title: Decreased Coenzyme Q10 Levels in Multiple System Atrophy Cerebellum.
abstract: In familial and sporadic multiple system atrophy (MSA) patients, deficiency of coenzyme Q10 (CoQ10) has been associated with mutations in COQ2, which encodes the second enzyme in the CoQ10 biosynthetic pathway. Cerebellar ataxia is the most common presentation of CoQ10 deficiency, suggesting that the cerebellum might be selectively vulnerable to low levels of CoQ10 To investigate whether CoQ10 deficiency represents a common feature in the brains of MSA patients independent of the presence of COQ2 mutations, we studied CoQ10 levels in postmortem brains of 12 MSA, 9 Parkinson disease (PD), 9 essential tremor (ET) patients, and 12 controls. We also assessed mitochondrial respiratory chain enzyme activities, oxidative stress, mitochondrial mass, and levels of enzymes involved in CoQ biosynthesis. Our studies revealed CoQ10 deficiency in MSA cerebellum, which was associated with impaired CoQ biosynthesis and increased oxidative stress in the absence of COQ2 mutations. The levels of CoQ10 in the cerebella of ET and PD patients were comparable or higher than in controls. These findings suggest that CoQ10 deficiency may contribute to the pathogenesis of MSA. Because no disease modifying therapies are currently available, increasing CoQ10 levels by supplementation or upregulation of its biosynthesis may represent a novel treatment strategy for MSA patients.
authors.affiliation: From the Department of Neurology, College of Physicians and Surgeons, Columbia University, New York (EB, GK, GT, MZ, ST, UJK, S-HK, CMQ); UOC of Neurology and Neuromuscular Disorders, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy (EB); Department of Neuroscience and Pathology, University of California, San Diego, California (EM); Department of Neurology, Yale School of Medicine, Yale University, New Haven, Connecticut (EDL); Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, Connecticut (EDL); Center for Neuroepidemiology and Clinical Neurological Research, Yale School of Medicine, Yale University, New Haven, Connecticut (EDL); Department of Pathology and Cell Biology, Columbia University Medical Center and the New York Presbyterian Hospital, New York (PF, JT, EPC, J-PGV); and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York (JT, EPC, J-PGV).
authors.forename: Emanuele
authors.initials: E
authors.lastname: Barca
authors.affiliation: From the Department of Neurology, College of Physicians and Surgeons, Columbia University, New York (EB, GK, GT, MZ, ST, UJK, S-HK, CMQ); UOC of Neurology and Neuromuscular Disorders, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy (EB); Department of Neuroscience and Pathology, University of California, San Diego, California (EM); Department of Neurology, Yale School of Medicine, Yale University, New Haven, Connecticut (EDL); Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, Connecticut (EDL); Center for Neuroepidemiology and Clinical Neurological Research, Yale School of Medicine, Yale University, New Haven, Connecticut (EDL); Department of Pathology and Cell Biology, Columbia University Medical Center and the New York Presbyterian Hospital, New York (PF, JT, EPC, J-PGV); and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York (JT, EPC, J-PGV).
authors.forename: Giulio
authors.initials: G
authors.lastname: Kleiner
authors.affiliation: From the Department of Neurology, College of Physicians and Surgeons, Columbia University, New York (EB, GK, GT, MZ, ST, UJK, S-HK, CMQ); UOC of Neurology and Neuromuscular Disorders, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy (EB); Department of Neuroscience and Pathology, University of California, San Diego, California (EM); Department of Neurology, Yale School of Medicine, Yale University, New Haven, Connecticut (EDL); Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, Connecticut (EDL); Center for Neuroepidemiology and Clinical Neurological Research, Yale School of Medicine, Yale University, New Haven, Connecticut (EDL); Department of Pathology and Cell Biology, Columbia University Medical Center and the New York Presbyterian Hospital, New York (PF, JT, EPC, J-PGV); and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York (JT, EPC, J-PGV).
authors.forename: Guomei
authors.initials: G
authors.lastname: Tang
authors.affiliation: From the Department of Neurology, College of Physicians and Surgeons, Columbia University, New York (EB, GK, GT, MZ, ST, UJK, S-HK, CMQ); UOC of Neurology and Neuromuscular Disorders, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy (EB); Department of Neuroscience and Pathology, University of California, San Diego, California (EM); Department of Neurology, Yale School of Medicine, Yale University, New Haven, Connecticut (EDL); Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, Connecticut (EDL); Center for Neuroepidemiology and Clinical Neurological Research, Yale School of Medicine, Yale University, New Haven, Connecticut (EDL); Department of Pathology and Cell Biology, Columbia University Medical Center and the New York Presbyterian Hospital, New York (PF, JT, EPC, J-PGV); and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York (JT, EPC, J-PGV).
authors.forename: Marcello
authors.initials: M
authors.lastname: Ziosi
authors.affiliation: From the Department of Neurology, College of Physicians and Surgeons, Columbia University, New York (EB, GK, GT, MZ, ST, UJK, S-HK, CMQ); UOC of Neurology and Neuromuscular Disorders, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy (EB); Department of Neuroscience and Pathology, University of California, San Diego, California (EM); Department of Neurology, Yale School of Medicine, Yale University, New Haven, Connecticut (EDL); Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, Connecticut (EDL); Center for Neuroepidemiology and Clinical Neurological Research, Yale School of Medicine, Yale University, New Haven, Connecticut (EDL); Department of Pathology and Cell Biology, Columbia University Medical Center and the New York Presbyterian Hospital, New York (PF, JT, EPC, J-PGV); and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York (JT, EPC, J-PGV).
authors.forename: Saba
authors.initials: S
authors.lastname: Tadesse
authors.affiliation: From the Department of Neurology, College of Physicians and Surgeons, Columbia University, New York (EB, GK, GT, MZ, ST, UJK, S-HK, CMQ); UOC of Neurology and Neuromuscular Disorders, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy (EB); Department of Neuroscience and Pathology, University of California, San Diego, California (EM); Department of Neurology, Yale School of Medicine, Yale University, New Haven, Connecticut (EDL); Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, Connecticut (EDL); Center for Neuroepidemiology and Clinical Neurological Research, Yale School of Medicine, Yale University, New Haven, Connecticut (EDL); Department of Pathology and Cell Biology, Columbia University Medical Center and the New York Presbyterian Hospital, New York (PF, JT, EPC, J-PGV); and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York (JT, EPC, J-PGV).
authors.forename: Eliezer
authors.initials: E
authors.lastname: Masliah
authors.affiliation: From the Department of Neurology, College of Physicians and Surgeons, Columbia University, New York (EB, GK, GT, MZ, ST, UJK, S-HK, CMQ); UOC of Neurology and Neuromuscular Disorders, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy (EB); Department of Neuroscience and Pathology, University of California, San Diego, California (EM); Department of Neurology, Yale School of Medicine, Yale University, New Haven, Connecticut (EDL); Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, Connecticut (EDL); Center for Neuroepidemiology and Clinical Neurological Research, Yale School of Medicine, Yale University, New Haven, Connecticut (EDL); Department of Pathology and Cell Biology, Columbia University Medical Center and the New York Presbyterian Hospital, New York (PF, JT, EPC, J-PGV); and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York (JT, EPC, J-PGV).
authors.forename: Elan D
authors.initials: ED
authors.lastname: Louis
authors.affiliation: From the Department of Neurology, College of Physicians and Surgeons, Columbia University, New York (EB, GK, GT, MZ, ST, UJK, S-HK, CMQ); UOC of Neurology and Neuromuscular Disorders, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy (EB); Department of Neuroscience and Pathology, University of California, San Diego, California (EM); Department of Neurology, Yale School of Medicine, Yale University, New Haven, Connecticut (EDL); Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, Connecticut (EDL); Center for Neuroepidemiology and Clinical Neurological Research, Yale School of Medicine, Yale University, New Haven, Connecticut (EDL); Department of Pathology and Cell Biology, Columbia University Medical Center and the New York Presbyterian Hospital, New York (PF, JT, EPC, J-PGV); and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York (JT, EPC, J-PGV).
authors.forename: Phyllis
authors.initials: P
authors.lastname: Faust
authors.affiliation: From the Department of Neurology, College of Physicians and Surgeons, Columbia University, New York (EB, GK, GT, MZ, ST, UJK, S-HK, CMQ); UOC of Neurology and Neuromuscular Disorders, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy (EB); Department of Neuroscience and Pathology, University of California, San Diego, California (EM); Department of Neurology, Yale School of Medicine, Yale University, New Haven, Connecticut (EDL); Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, Connecticut (EDL); Center for Neuroepidemiology and Clinical Neurological Research, Yale School of Medicine, Yale University, New Haven, Connecticut (EDL); Department of Pathology and Cell Biology, Columbia University Medical Center and the New York Presbyterian Hospital, New York (PF, JT, EPC, J-PGV); and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York (JT, EPC, J-PGV).
authors.forename: Un J
authors.initials: UJ
authors.lastname: Kang
authors.affiliation: From the Department of Neurology, College of Physicians and Surgeons, Columbia University, New York (EB, GK, GT, MZ, ST, UJK, S-HK, CMQ); UOC of Neurology and Neuromuscular Disorders, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy (EB); Department of Neuroscience and Pathology, University of California, San Diego, California (EM); Department of Neurology, Yale School of Medicine, Yale University, New Haven, Connecticut (EDL); Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, Connecticut (EDL); Center for Neuroepidemiology and Clinical Neurological Research, Yale School of Medicine, Yale University, New Haven, Connecticut (EDL); Department of Pathology and Cell Biology, Columbia University Medical Center and the New York Presbyterian Hospital, New York (PF, JT, EPC, J-PGV); and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York (JT, EPC, J-PGV).
authors.forename: Jose
authors.initials: J
authors.lastname: Torres
authors.affiliation: From the Department of Neurology, College of Physicians and Surgeons, Columbia University, New York (EB, GK, GT, MZ, ST, UJK, S-HK, CMQ); UOC of Neurology and Neuromuscular Disorders, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy (EB); Department of Neuroscience and Pathology, University of California, San Diego, California (EM); Department of Neurology, Yale School of Medicine, Yale University, New Haven, Connecticut (EDL); Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, Connecticut (EDL); Center for Neuroepidemiology and Clinical Neurological Research, Yale School of Medicine, Yale University, New Haven, Connecticut (EDL); Department of Pathology and Cell Biology, Columbia University Medical Center and the New York Presbyterian Hospital, New York (PF, JT, EPC, J-PGV); and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York (JT, EPC, J-PGV).
authors.forename: Etty P
authors.initials: EP
authors.lastname: Cortes
authors.affiliation: From the Department of Neurology, College of Physicians and Surgeons, Columbia University, New York (EB, GK, GT, MZ, ST, UJK, S-HK, CMQ); UOC of Neurology and Neuromuscular Disorders, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy (EB); Department of Neuroscience and Pathology, University of California, San Diego, California (EM); Department of Neurology, Yale School of Medicine, Yale University, New Haven, Connecticut (EDL); Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, Connecticut (EDL); Center for Neuroepidemiology and Clinical Neurological Research, Yale School of Medicine, Yale University, New Haven, Connecticut (EDL); Department of Pathology and Cell Biology, Columbia University Medical Center and the New York Presbyterian Hospital, New York (PF, JT, EPC, J-PGV); and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York (JT, EPC, J-PGV).
authors.forename: Jean-Paul G
authors.initials: JP
authors.lastname: Vonsattel
authors.affiliation: From the Department of Neurology, College of Physicians and Surgeons, Columbia University, New York (EB, GK, GT, MZ, ST, UJK, S-HK, CMQ); UOC of Neurology and Neuromuscular Disorders, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy (EB); Department of Neuroscience and Pathology, University of California, San Diego, California (EM); Department of Neurology, Yale School of Medicine, Yale University, New Haven, Connecticut (EDL); Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, Connecticut (EDL); Center for Neuroepidemiology and Clinical Neurological Research, Yale School of Medicine, Yale University, New Haven, Connecticut (EDL); Department of Pathology and Cell Biology, Columbia University Medical Center and the New York Presbyterian Hospital, New York (PF, JT, EPC, J-PGV); and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York (JT, EPC, J-PGV).
authors.forename: Sheng-Han
authors.initials: SH
authors.lastname: Kuo
authors.affiliation: From the Department of Neurology, College of Physicians and Surgeons, Columbia University, New York (EB, GK, GT, MZ, ST, UJK, S-HK, CMQ); UOC of Neurology and Neuromuscular Disorders, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy (EB); Department of Neuroscience and Pathology, University of California, San Diego, California (EM); Department of Neurology, Yale School of Medicine, Yale University, New Haven, Connecticut (EDL); Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, Connecticut (EDL); Center for Neuroepidemiology and Clinical Neurological Research, Yale School of Medicine, Yale University, New Haven, Connecticut (EDL); Department of Pathology and Cell Biology, Columbia University Medical Center and the New York Presbyterian Hospital, New York (PF, JT, EPC, J-PGV); and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York (JT, EPC, J-PGV). sk3295@columbia.edu.
authors.forename: Catarina M
authors.initials: CM
authors.lastname: Quinzii
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001259:Ataxia / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D002531:Cerebellum / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D019578:Multiple System Atrophy / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D018908:Muscle Weakness / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000172:deficiency* / Q000378:metabolism
chemical_list: D014451:Ubiquinone; C024989:coenzyme Q10
keywords: Cerebellar ataxia; Coenzyme Q10; Multiple system atrophy; Oxidative stress