A Double-Pronged Sword: XJB-5-131 Is a Suppressor of Somatic Instability and Toxicity in Huntington’s Disease

Wipf, Pater; Polyzos, Aris A.; McMurray, Cynthia T.

doi:10.3233/jhd-210510

Title: A Double-Pronged Sword: XJB-5-131 Is a Suppressor of Somatic Instability and Toxicity in Huntington’s Disease

Journal Article · 28 February 2022 · Journal of Huntington's Disease

DOI: https://doi.org/10.3233/jhd-210510 · OSTI ID:1892178

Wipf, Pater ^[1]; Polyzos, Aris A. ^[2]; McMurray, Cynthia T. ^[2]

Univ. of Pittsburgh, PA (United States)
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Molecular Biophysics and Integrated Bioimaging

Due to large increases in the elderly populations across the world, age-related diseases are expected to expand dramatically in the coming years. Among these, neurodegenerative diseases will be among the most devastating in terms of their emotional and economic impact on patients, their families, and associated subsidized health costs. There is no currently available cure or rescue for dying brain cells. Viable therapeutics for any of these disorders would be a breakthrough and provide relief for the large number of affected patients and their families. Neurodegeneration is accompanied by elevated oxidative damage and inflammation. While natural antioxidants have largely failed in clinical trials, preclinical phenotyping of the unnatural, mitochondrial targeted nitroxide, XJB-5-131, bodes well for further translational development in advanced animal models or in humans. Here we consider the usefulness of synthetic antioxidants for the treatment of Huntington’s disease. The mitochondrial targeting properties of XJB-5-131 have great promise. It is both an electron scavenger and an antioxidant, reducing both somatic expansion and toxicity simultaneously through the same redox mechanism. By quenching reactive oxygen species, XJB-5-131 breaks the cycle between the rise in oxidative damage during disease progression and the somatic growth of the CAG repeat which depends on oxidation.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: National Institutes of Health; USDOE Office of Science (SC)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1892178

Journal Information:: Journal of Huntington's Disease, Journal Name: Journal of Huntington's Disease Journal Issue: 1 Vol. 11; ISSN 1879-6397

Publisher:: IOS PressCopyright Statement

Country of Publication:: United States

Language:: English

References (98)

Heterogeneity of Coenzyme Q₁₀Deficiency Emmanuele, Valentina; López, Luis C.; Berardo, Andres Archives of Neurology, Vol. 69, Issue 8 https://doi.org/10.1001/archneurol.2012.206	journal	August 2012
A Randomized Clinical Trial of High-Dosage Coenzyme Q10 in Early Parkinson Disease: No Evidence of Benefit Beal, M. Flint; Oakes, David; Shoulson, Ira JAMA Neurology, Vol. 71, Issue 5 https://doi.org/10.1001/jamaneurol.2014.131	journal	May 2014
The Mismatch Repair Protein MSH2 is Rate Limiting for Repeat Expansion in a Fragile X Premutation Mouse Model Lokanga, Rachel Adihe; Zhao, Xiao-Nan; Usdin, Karen Human Mutation, Vol. 35, Issue 1 https://doi.org/10.1002/humu.22464	journal	November 2013
Mitochondrial-derived reactive oxygen species (ROS) play a causal role in aging-related intervertebral disc degeneration: INTERVETEBRAL DISC OXIDATIVE DAMAGE Nasto, Luigi A.; Robinson, Andria R.; Ngo, Kevin Journal of Orthopaedic Research, Vol. 31, Issue 7 https://doi.org/10.1002/jor.22320	journal	February 2013
Targeting Expanded Repeats by Small Molecules in Repeat Expansion Disorders Nakamori, Masayuki; Mochizuki, Hideki Movement Disorders, Vol. 36, Issue 2 https://doi.org/10.1002/mds.28397	journal	December 2020
Management of oxidative stress and other pathologies in Alzheimer’s disease Simunkova, Miriama; Alwasel, Saleh H.; Alhazza, Ibrahim M. Archives of Toxicology, Vol. 93, Issue 9 https://doi.org/10.1007/s00204-019-02538-y	journal	August 2019
Reactive Oxygen Species: Beyond Their Reactive Behavior Tauffenberger, Arnaud; Magistretti, Pierre J. Neurochemical Research, Vol. 46, Issue 1 https://doi.org/10.1007/s11064-020-03208-7	journal	January 2021
A Novel Pharmacological Protective Role for Safranal in an Animal Model of Huntington’s Disease Fotoohi, Ahmad; Moloudi, Mohammad Raman; Hosseini, Saed Neurochemical Research, Vol. 46, Issue 6 https://doi.org/10.1007/s11064-021-03271-8	journal	February 2021
Antioxidant Combo Therapy Protects White Matter After Traumatic Brain Injury Chandran, Raghavendar; Mehta, Suresh L.; Vemuganti, Raghu NeuroMolecular Medicine, Vol. 23, Issue 3 https://doi.org/10.1007/s12017-021-08645-3	journal	January 2021
Coenzyme Q10 and remacemide hydrochloride ameliorate motor deficits in a Huntington's disease transgenic mouse model Schilling, Gabriele; Coonfield, Michael L.; Ross, Christopher A. Neuroscience Letters, Vol. 315, Issue 3 https://doi.org/10.1016/S0304-3940(01)02326-6	journal	November 2001
Effects of coenzyme Q10 administration on its tissue concentrations, mitochondrial oxidant generation, and oxidative stress in the rat Kwong, Linda K.; Kamzalov, Sergey; Rebrin, Igor Free Radical Biology and Medicine, Vol. 33, Issue 5 https://doi.org/10.1016/S0891-5849(02)00916-4	journal	September 2002
Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study Moss, Davina J. Hensman; Pardiñas, Antonio F.; Langbehn, Douglas The Lancet Neurology, Vol. 16, Issue 9 https://doi.org/10.1016/S1474-4422(17)30161-8	journal	September 2017
Oral Coenzyme Q10 Supplementation in Patients with Nonalcoholic Fatty Liver Disease: Effects on Serum Vaspin, Chemerin, Pentraxin 3, Insulin Resistance and Oxidative Stress Farhangi, Mahdieh Abbasalizad; Alipour, Beytollah; Jafarvand, Elnaz Archives of Medical Research, Vol. 45, Issue 7 https://doi.org/10.1016/j.arcmed.2014.11.001	journal	October 2014
Conditional ablation of reactive astrocytes to dissect their roles in spinal cord injury and repair Gu, Yakun; Cheng, Xueyan; Huang, Xiao Brain, Behavior, and Immunity, Vol. 80 https://doi.org/10.1016/j.bbi.2019.04.016	journal	August 2019
Hemigramicidin–TEMPO conjugates: Novel mitochondria-targeted anti-oxidants Fink, Mitchell P.; Macias, Carlos A.; Xiao, Jingbo Biochemical Pharmacology, Vol. 74, Issue 6 https://doi.org/10.1016/j.bcp.2007.05.019	journal	September 2007
Identification of Genetic Factors that Modify Clinical Onset of Huntington’s Disease Lee, Jong-Min; Wheeler, Vanessa C.; Chao, Michael J. Cell, Vol. 162, Issue 3 https://doi.org/10.1016/j.cell.2015.07.003	journal	July 2015
CAG Repeat Not Polyglutamine Length Determines Timing of Huntington’s Disease Onset Lee, Jong-Min; Correia, Kevin; Loupe, Jacob Cell, Vol. 178, Issue 4 https://doi.org/10.1016/j.cell.2019.06.036	journal	August 2019
Targeting of XJB-5-131 to Mitochondria Suppresses Oxidative DNA Damage and Motor Decline in a Mouse Model of Huntington’s Disease Xun, Zhiyin; Rivera-Sánchez, Sulay; Ayala-Peña, Sylvette Cell Reports, Vol. 2, Issue 5 https://doi.org/10.1016/j.celrep.2012.10.001	journal	November 2012
Thermoregulatory and metabolic defects in Huntington's disease transgenic mice implicate PGC-1α in Huntington's disease neurodegeneration Weydt, Patrick; Pineda, Victor V.; Torrence, Anne E. Cell Metabolism, Vol. 4, Issue 5 https://doi.org/10.1016/j.cmet.2006.10.004	journal	November 2006
Metabolic Reprogramming in Astrocytes Distinguishes Region-Specific Neuronal Susceptibility in Huntington Mice Polyzos, Aris A.; Lee, Do Yup; Datta, Rupsa Cell Metabolism, Vol. 29, Issue 6 https://doi.org/10.1016/j.cmet.2019.03.004	journal	June 2019
Secondary coenzyme Q deficiency in neurological disorders Gueguen, Naig; Baris, Olivier; Lenaers, Guy Free Radical Biology and Medicine, Vol. 165 https://doi.org/10.1016/j.freeradbiomed.2021.01.017	journal	March 2021
Evaluation of cytotoxicity of oils used in coenzyme Q10 Self-Emulsifying Drug Delivery Systems (SEDDS) Palamakula, Anitha; Khan, Mansoor A. International Journal of Pharmaceutics, Vol. 273, Issue 1-2 https://doi.org/10.1016/j.ijpharm.2003.12.010	journal	April 2004
The chicken or the egg: mitochondrial dysfunction as a cause or consequence of toxicity in Huntington’s disease Polyzos, Aris A.; McMurray, Cynthia T. Mechanisms of Ageing and Development, Vol. 161 https://doi.org/10.1016/j.mad.2016.09.003	journal	January 2017
Coenzyme Q10 supplementation – In ageing and disease Aaseth, Jan; Alexander, Jan; Alehagen, Urban Mechanisms of Ageing and Development, Vol. 197 https://doi.org/10.1016/j.mad.2021.111521	journal	July 2021
Evidence for behavioral benefits of early dietary supplementation with CoEnzymeQ10 in a slowly progressing mouse model of Huntington's disease Hickey, Miriam A.; Zhu, Chunni; Medvedeva, Vera Molecular and Cellular Neuroscience, Vol. 49, Issue 2 https://doi.org/10.1016/j.mcn.2011.10.007	journal	February 2012
Small molecules as therapeutic drugs for Alzheimer's disease Oliver, Darryll M. A.; Reddy, P. Hemachandra Molecular and Cellular Neuroscience, Vol. 96 https://doi.org/10.1016/j.mcn.2019.03.001	journal	April 2019
Coenzyme Q, oxidative stress and aging Sohal, Rajindar S.; Forster, Michael J. Mitochondrion, Vol. 7 https://doi.org/10.1016/j.mito.2007.03.006	journal	June 2007
Intergenerational and striatal CAG repeat instability in Huntington's disease knock-in mice involve different DNA repair genes Dragileva, Ella; Hendricks, Audrey; Teed, Allison Neurobiology of Disease, Vol. 33, Issue 1 https://doi.org/10.1016/j.nbd.2008.09.014	journal	January 2009
Advancing the health of our aging population: A lead role for nursing science Grady, Patricia A. Nursing Outlook, Vol. 59, Issue 4 https://doi.org/10.1016/j.outlook.2011.05.017	journal	July 2011
Regulation of hepatic coenzyme Q biosynthesis by dietary omega-3 polyunsaturated fatty acids Fernández-del-Río, Lucía; Rodríguez-López, Sandra; Gutiérrez-Casado, Elena Redox Biology, Vol. 46 https://doi.org/10.1016/j.redox.2021.102061	journal	October 2021
Protective Effect of Natural Products against Huntington’s Disease: An Overview of Scientific Evidence and Understanding Their Mechanism of Action Lum, Pei Teng; Sekar, Mahendran; Gan, Siew Hua ACS Chemical Neuroscience, Vol. 12, Issue 3 https://doi.org/10.1021/acschemneuro.0c00824	journal	January 2021
Targeting Mitochondria Hoye, Adam T.; Davoren, Jennifer E.; Wipf, Peter Accounts of Chemical Research, Vol. 41, Issue 1 https://doi.org/10.1021/ar700135m	journal	January 2008
Superoxide Dismutases and Superoxide Reductases Sheng, Yuewei; Abreu, Isabel A.; Cabelli, Diane E. Chemical Reviews, Vol. 114, Issue 7 https://doi.org/10.1021/cr4005296	journal	January 2014
Mitochondrial Targeting of Selective Electron Scavengers: Synthesis and Biological Analysis of Hemigramicidin−TEMPO Conjugates Wipf, Peter; Xiao, Jingbo; Jiang, Jianfei Journal of the American Chemical Society, Vol. 127, Issue 36 https://doi.org/10.1021/ja053679l	journal	September 2005
Characterization of Hydantoin Products from One-Electron Oxidation of 8-Oxo-7,8-dihydroguanosine in a Nucleoside Model Luo, Wenchen; Muller, James G.; Rachlin, Elliot M. Chemical Research in Toxicology, Vol. 14, Issue 7 https://doi.org/10.1021/tx010072j	journal	July 2001
Pivotal Role for Two Electron Reduction in 2,3-Dimethoxy-1,4-naphthoquinone and 2-Methyl-1,4-naphthoquinone Metabolism and Kinetics in Vivo That Prevents Liver Redox Stress Parry, Joel D.; Pointon, Amy V.; Lutz, Ursula Chemical Research in Toxicology, Vol. 22, Issue 4 https://doi.org/10.1021/tx800472z	journal	April 2009
Msh2 deficiency prevents in vivo somatic instability of the CAG repeat in Huntington disease transgenic mice Manley, Kevin; Shirley, Thomas L.; Flaherty, Lorraine Nature Genetics, Vol. 23, Issue 4 https://doi.org/10.1038/70598	journal	December 1999
MutSβ promotes trinucleotide repeat expansion by recruiting DNA polymerase β to nascent (CAG)n or (CTG)n hairpins for error-prone DNA synthesis Guo, Jinzhen; Gu, Liya; Leffak, Michael Cell Research, Vol. 26, Issue 7 https://doi.org/10.1038/cr.2016.66	journal	June 2016
Double setback for ASO trials in Huntington disease Kingwell, Katie Nature Reviews Drug Discovery, Vol. 20, Issue 6 https://doi.org/10.1038/d41573-021-00088-6	journal	May 2021
Failure of genetic therapies for Huntington’s devastates community Kwon, Diana Nature, Vol. 593, Issue 7858 https://doi.org/10.1038/d41586-021-01177-7	journal	May 2021
OGG1 initiates age-dependent CAG trinucleotide expansion in somatic cells Kovtun, Irina V.; Liu, Yuan; Bjoras, Magnar Nature, Vol. 447, Issue 7143 https://doi.org/10.1038/nature05778	journal	April 2007
Crosstalk between MSH2–MSH3 and polβ promotes trinucleotide repeat expansion during base excision repair Lai, Yanhao; Budworth, Helen; Beaver, Jill M. Nature Communications, Vol. 7, Issue 1 https://doi.org/10.1038/ncomms12465	journal	August 2016
Lipidomics identifies cardiolipin oxidation as a mitochondrial target for redox therapy of brain injury Ji, Jing; Kline, Anthony E.; Amoscato, Andrew Nature Neuroscience, Vol. 15, Issue 10 https://doi.org/10.1038/nn.3195	journal	August 2012
(CAG)n-hairpin DNA binds to Msh2–Msh3 and changes properties of mismatch recognition Owen, Barbara A. L.; Yang, Zungyoon; Lai, Maoyi Nature Structural & Molecular Biology, Vol. 12, Issue 8 https://doi.org/10.1038/nsmb965	journal	July 2005
XJB-5-131 inhibited ferroptosis in tubular epithelial cells after ischemia−reperfusion injury Zhao, Zhi; Wu, Jianliang; Xu, Huzi Cell Death & Disease, Vol. 11, Issue 8 https://doi.org/10.1038/s41419-020-02871-6	journal	August 2020
Prevalence of Parkinson’s disease across North America Marras, C.; Beck, J. C.; Bower, J. H. npj Parkinson's Disease, Vol. 4, Issue 1 https://doi.org/10.1038/s41531-018-0058-0	journal	July 2018
Plasma coenzyme Q10 status is impaired in selected genetic conditions Montero, Raquel; Yubero, Delia; Salgado, Maria C. Scientific Reports, Vol. 9, Issue 1 https://doi.org/10.1038/s41598-018-37542-2	journal	January 2019
Extrahelical (CAG)/(CTG) triplet repeat elements support proliferating cell nuclear antigen loading and MutL endonuclease activation Pluciennik, A.; Burdett, V.; Baitinger, C. Proceedings of the National Academy of Sciences, Vol. 110, Issue 30 https://doi.org/10.1073/pnas.1311325110	journal	July 2013
Human MutLγ, the MLH1–MLH3 heterodimer, is an endonuclease that promotes DNA expansion Kadyrova, Lyudmila Y.; Gujar, Vaibhavi; Burdett, Vickers Proceedings of the National Academy of Sciences, Vol. 117, Issue 7 https://doi.org/10.1073/pnas.1914718117	journal	February 2020
Coordination between Polymerase β and FEN1 Can Modulate CAG Repeat Expansion Liu, Yuan; Prasad, Rajendra; Beard, William A. Journal of Biological Chemistry, Vol. 284, Issue 41 https://doi.org/10.1074/jbc.M109.050286	journal	August 2009
Emerging therapeutics in Huntington’s disease Wiggins, Robert; Feigin, Andrew Expert Opinion on Emerging Drugs, Vol. 26, Issue 3 https://doi.org/10.1080/14728214.2021.1962285	journal	July 2021
Coenzyme Q₁₀ and the exclusive club of diseases that show a limited response to treatment Turton, Nadia; Bowers, Nathan; Khajeh, Sam Expert Opinion on Orphan Drugs, Vol. 9, Issue 5 https://doi.org/10.1080/21678707.2021.1932459	journal	May 2021
CTG repeat instability and size variation timing in DNA repair-deficient mice Savouret, C. The EMBO Journal, Vol. 22, Issue 9 https://doi.org/10.1093/emboj/cdg202	journal	May 2003
Neurological abnormalities in a knock-in mouse model of Huntington's disease Lin, C. -H. Human Molecular Genetics, Vol. 10, Issue 2 https://doi.org/10.1093/hmg/10.2.137	journal	January 2001
Somatic expansion behaviour of the (CTG)n repeat in myotonic dystrophy knock-in mice is differentially affected by Msh3 and Msh6 mismatch-repair proteins van den Broek, W. J. A. A. Human Molecular Genetics, Vol. 11, Issue 2 https://doi.org/10.1093/hmg/11.2.191	journal	January 2002
Long glutamine tracts cause nuclear localization of a novel form of huntingtin in medium spiny striatal neurons in HdhQ92 and HdhQ111 knock-in mice Wheeler, V. C. Human Molecular Genetics, Vol. 9, Issue 4 https://doi.org/10.1093/hmg/9.4.503	journal	March 2000
Mitochondrial targeting of XJB-5-131 attenuates or improves pathophysiology in HdhQ150 animals with well-developed disease phenotypes Polyzos, Aris; Holt, Amy; Brown, Christopher Human Molecular Genetics, Vol. 25, Issue 9 https://doi.org/10.1093/hmg/ddw051	journal	February 2016
A modifier of Huntington's disease onset at the MLH1 locus Lee, Jong-Min; Chao, Michael J.; Harold, Denise Human Molecular Genetics, Vol. 26, Issue 19 https://doi.org/10.1093/hmg/ddx286	journal	July 2017
Somatic CAG expansion in Huntington's disease is dependent on the MLH3 endonuclease domain, which can be excluded via splice redirection Roy, Jennie C. L.; Vitalo, Antonia; Andrew, Marissa A. Nucleic Acids Research, Vol. 49, Issue 7 https://doi.org/10.1093/nar/gkab152	journal	March 2021
Perfluorooctane Sulfonate (PFOS) Produces Dopaminergic Neuropathology in Caenorhabditis elegans Sammi, Shreesh Raj; Foguth, Rachel M.; Nieves, Claudia Sofía Toxicological Sciences, Vol. 172, Issue 2 https://doi.org/10.1093/toxsci/kfz191	journal	August 2019
Mitochondria‐targeted antioxidants protect Friedreich Ataxia fibroblasts from endogenous oxidative stress more effectively than untargeted antioxidants Jauslin, Matthias L.; Meier, Thomas; Smith, Robin A. J. The FASEB Journal, Vol. 17, Issue 13 https://doi.org/10.1096/fj.03-0240fje	journal	August 2003
Mitochondria‐targeted antioxidants Oyewole, Anne O.; Birch‐Machin, Mark A. The FASEB Journal, Vol. 29, Issue 12 https://doi.org/10.1096/fj.15-275404	journal	August 2015
Treatment With a Novel Hemigramicidin-TEMPO Conjugate Prolongs Survival in a Rat Model of Lethal Hemorrhagic Shock Macias, Carlos A.; Chiao, Jeffrey W.; Xiao, Jingbo Annals of Surgery, Vol. 245, Issue 2 https://doi.org/10.1097/01.sla.0000236626.57752.8e	journal	January 2007
Coenzyme Q10 supplementation: Efficacy, safety, and formulation challenges Arenas‐Jal, Marta; Suñé‐Negre, J. M.; García‐Montoya, Encarna Comprehensive Reviews in Food Science and Food Safety, Vol. 19, Issue 2 https://doi.org/10.1111/1541-4337.12539	journal	February 2020
Huntington's disease: a clinical review McColgan, P.; Tabrizi, S. J. European Journal of Neurology, Vol. 25, Issue 1 https://doi.org/10.1111/ene.13413	journal	September 2017
Bioenergetic analysis of isolated cerebrocortical nerve terminals on a microgram scale: spare respiratory capacity and stochastic mitochondrial failure Choi, Sung W.; Gerencser, Akos A.; Nicholls, David G. Journal of Neurochemistry, Vol. 109, Issue 4 https://doi.org/10.1111/j.1471-4159.2009.06055.x	journal	May 2009
Combination therapy with Coenzyme Q₁₀and creatine produces additive neuroprotective effects in models of Parkinson’s and Huntington’s Diseases Yang, Lichuan; Calingasan, Noel Y.; Wille, Elizabeth J. Journal of Neurochemistry, Vol. 109, Issue 5 https://doi.org/10.1111/j.1471-4159.2009.06074.x	journal	June 2009
Mitochondrial-Targeted Antioxidants Attenuate TGF-β2 Signaling in Human Trabecular Meshwork Cells Rao, Vidhya R.; Lautz, Jonathan D.; Kaja, Simon Investigative Opthalmology & Visual Science, Vol. 60, Issue 10 https://doi.org/10.1167/iovs.19-27542	journal	August 2019
A randomized clinical trial of coenzyme Q10 and GPI-1485 in early Parkinson disease Neurology, Vol. 68, Issue 1 https://doi.org/10.1212/01.wnl.0000250355.28474.8e	journal	January 2007
A randomized, double-blind, placebo-controlled trial of coenzyme Q10 in Huntington disease McGarry, Andrew; McDermott, Michael; Kieburtz, Karl Neurology, Vol. 88, Issue 2 https://doi.org/10.1212/WNL.0000000000003478	journal	December 2016
A randomized, placebo-controlled trial of coenzyme Q₁₀ and remacemide in Huntington’s disease Neurology, Vol. 57, Issue 3 https://doi.org/10.1212/WNL.57.3.397	journal	August 2001
Effects of Anthocyanins on CAG Repeat Instability and Behaviour in Huntington’s Disease R6/1 Mice Møllersen, Linda; Moldestad, Olve; Rowe, Alexander D. PLoS Currents https://doi.org/10.1371/currents.hd.58d04209ab6d5de0844db7ef5628ff67	journal	January 2016
Deletion of the Huntingtin Polyglutamine Stretch Enhances Neuronal Autophagy and Longevity in Mice Zheng, Shuqiu; Clabough, Erin B. D.; Sarkar, Sovan PLoS Genetics, Vol. 6, Issue 2 https://doi.org/10.1371/journal.pgen.1000838	journal	February 2010
MSH3 Polymorphisms and Protein Levels Affect CAG Repeat Instability in Huntington's Disease Mice Tomé, Stéphanie; Manley, Kevin; Simard, Jodie P. PLoS Genetics, Vol. 9, Issue 2 https://doi.org/10.1371/journal.pgen.1003280	journal	February 2013
Mismatch Repair Genes Mlh1 and Mlh3 Modify CAG Instability in Huntington's Disease Mice: Genome-Wide and Candidate Approaches Pinto, Ricardo Mouro; Dragileva, Ella; Kirby, Andrew PLoS Genetics, Vol. 9, Issue 10 https://doi.org/10.1371/journal.pgen.1003930	journal	October 2013
Heterozygosity for a Hypomorphic Polβ Mutation Reduces the Expansion Frequency in a Mouse Model of the Fragile X-Related Disorders Lokanga, Rachel Adihe; Senejani, Alireza Ghodsi; Sweasy, Joann Balazs PLOS Genetics, Vol. 11, Issue 4 https://doi.org/10.1371/journal.pgen.1005181	journal	April 2015
Suppression of Somatic Expansion Delays the Onset of Pathophysiology in a Mouse Model of Huntington’s Disease Budworth, Helen; Harris, Faye R.; Williams, Paul PLOS Genetics, Vol. 11, Issue 8 https://doi.org/10.1371/journal.pgen.1005267	journal	August 2015
Comprehensive Behavioral Testing in the R6/2 Mouse Model of Huntington's Disease Shows No Benefit from CoQ10 or Minocycline Menalled, Liliana B.; Patry, Monica; Ragland, Natalie PLoS ONE, Vol. 5, Issue 3 https://doi.org/10.1371/journal.pone.0009793	journal	March 2010
Pms2 Suppresses Large Expansions of the (GAA·TTC)n Sequence in Neuronal Tissues Bourn, Rebecka L.; De Biase, Irene; Pinto, Ricardo Mouro PLoS ONE, Vol. 7, Issue 10 https://doi.org/10.1371/journal.pone.0047085	journal	October 2012
MutLα Heterodimers Modify the Molecular Phenotype of Friedreich Ataxia Ezzatizadeh, Vahid; Sandi, Chiranjeevi; Sandi, Madhavi PLoS ONE, Vol. 9, Issue 6 https://doi.org/10.1371/journal.pone.0100523	journal	June 2014
HdhQ111 Mice Exhibit Tissue Specific Metabolite Profiles that Include Striatal Lipid Accumulation Carroll, Jeffrey B.; Deik, Amy; Fossale, Elisa PLOS ONE, Vol. 10, Issue 8 https://doi.org/10.1371/journal.pone.0134465	journal	August 2015
XJB-5-131-mediated improvement in physiology and behaviour of the R6/2 mouse model of Huntington's disease is age- and sex- dependent Polyzos, Aris A.; Wood, Nigel I.; Williams, Paul PLOS ONE, Vol. 13, Issue 4 https://doi.org/10.1371/journal.pone.0194580	journal	April 2018
GS-Nitroxide (JP4-039)-Mediated Radioprotection of Human Fanconi Anemia Cell Lines Bernard, Mark E.; Kim, Hyun; Berhane, Hebist Radiation Research, Vol. 176, Issue 5 https://doi.org/10.1667/RR2624.1	journal	November 2011
Targeting Mitochondrial Dysfunction and Neurodegeneration by Means of Coenzyme Q10 and its Analogues Orsucci, D.; Mancuso, M.; Ienco, E. Caldarazzo Current Medicinal Chemistry, Vol. 18, Issue 26 https://doi.org/10.2174/092986711796957257	journal	September 2011
Do Naturally Occurring Antioxidants Protect Against Neurodegeneration of the Dopaminergic System? A Systematic Revision in Animal Models of Parkinson's Disease Costas, Carmen; Faro, Lilian R. F. Current Neuropharmacology, Vol. 20, Issue 2 https://doi.org/10.2174/1570159X19666210421092725	journal	February 2022
DNA Mismatch Repair and its Role in Huntington’s Disease Iyer, Ravi R.; Pluciennik, Anna Journal of Huntington's Disease, Vol. 10, Issue 1 https://doi.org/10.3233/JHD-200438	journal	February 2021
The Use of Coenzyme Q10 in Cardiovascular Diseases Rabanal-Ruiz, Yoana; Llanos-González, Emilio; Alcain, Francisco Javier Antioxidants, Vol. 10, Issue 5 https://doi.org/10.3390/antiox10050755	journal	May 2021
CoQ10 and Aging Barcelos, Isabella Peixoto de; Haas, Richard H. Biology, Vol. 8, Issue 2 https://doi.org/10.3390/biology8020028	journal	May 2019
Flavonoids: Potential Candidates for the Treatment of Neurodegenerative Disorders Devi, Shweta; Kumar, Vijay; Singh, Sandeep Kumar Biomedicines, Vol. 9, Issue 2 https://doi.org/10.3390/biomedicines9020099	journal	January 2021
Intracellular Sources of ROS/H2O2 in Health and Neurodegeneration: Spotlight on Endoplasmic Reticulum Konno, Tasuku; Melo, Eduardo Pinho; Chambers, Joseph E. Cells, Vol. 10, Issue 2 https://doi.org/10.3390/cells10020233	journal	January 2021
Disorders of Human Coenzyme Q10 Metabolism: An Overview Hargreaves, Iain; Heaton, Robert A.; Mantle, David International Journal of Molecular Sciences, Vol. 21, Issue 18 https://doi.org/10.3390/ijms21186695	journal	September 2020
Melatonin and Autophagy in Aging-Related Neurodegenerative Diseases Luo, Fang; Sandhu, Aaron F.; Rungratanawanich, Wiramon International Journal of Molecular Sciences, Vol. 21, Issue 19 https://doi.org/10.3390/ijms21197174	journal	September 2020
Cellular Consequences of Coenzyme Q10 Deficiency in Neurodegeneration of the Retina and Brain Manzar, Haider; Abdulhussein, Dalia; Yap, Timothy E. International Journal of Molecular Sciences, Vol. 21, Issue 23 https://doi.org/10.3390/ijms21239299	journal	December 2020
CoQ10 Deficient Endothelial Cell Culture Model for the Investigation of CoQ10 Blood–Brain Barrier Transport Wainwright, Luke; Hargreaves, Iain P.; Georgian, Ana R. Journal of Clinical Medicine, Vol. 9, Issue 10 https://doi.org/10.3390/jcm9103236	journal	October 2020
Silymarin in Combination with Vitamin C, Vitamin E, Coenzyme Q10 and Selenomethionine to Improve Liver Enzymes and Blood Lipid Profile in NAFLD Patients Curcio, Annalisa; Romano, Adriana; Cuozzo, Simona Medicina, Vol. 56, Issue 10 https://doi.org/10.3390/medicina56100544	journal	October 2020
Prolonged Intake of Coenzyme Q10 Impairs Cognitive Functions in Mice Sumien, Nathalie; Heinrich, Kevin R.; Shetty, Ritu A. The Journal of Nutrition, Vol. 139, Issue 10 https://doi.org/10.3945/jn.109.110437	journal	August 2009
Aducanumab: The first targeted Alzheimer's therapy Yang, Pan; Sun, Fusheng Drug Discoveries & Therapeutics, Vol. 15, Issue 3 https://doi.org/10.5582/ddt.2021.01061	journal	June 2021
Enrichment of coenzyme Q10 in plasma and blood cells: defense against oxidative damage Niklowitz, Petra; Sonnenschein, Anka; Janetzky, Bernd International Journal of Biological Sciences https://doi.org/10.7150/ijbs.3.257	journal	January 2007