{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T21:44:59Z","timestamp":1784756699638,"version":"3.55.0"},"reference-count":86,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T00:00:00Z","timestamp":1740700800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"#NEXTGENERATIONEU (NGEU)","award":["PE0000006"],"award-info":[{"award-number":["PE0000006"]}]},{"name":"#NEXTGENERATIONEU (NGEU)","award":["DN. 1553 11 October 2022"],"award-info":[{"award-number":["DN. 1553 11 October 2022"]}]},{"name":"#NEXTGENERATIONEU (NGEU)","award":["DM 352\/2022"],"award-info":[{"award-number":["DM 352\/2022"]}]},{"name":"#NEXTGENERATIONEU (NGEU)","award":["DM 117\/2023"],"award-info":[{"award-number":["DM 117\/2023"]}]},{"name":"Ministry of University and Research (MUR), National Recovery and Resilience Plan (NRRP)","award":["PE0000006"],"award-info":[{"award-number":["PE0000006"]}]},{"name":"Ministry of University and Research (MUR), National Recovery and Resilience Plan (NRRP)","award":["DN. 1553 11 October 2022"],"award-info":[{"award-number":["DN. 1553 11 October 2022"]}]},{"name":"Ministry of University and Research (MUR), National Recovery and Resilience Plan (NRRP)","award":["DM 352\/2022"],"award-info":[{"award-number":["DM 352\/2022"]}]},{"name":"Ministry of University and Research (MUR), National Recovery and Resilience Plan (NRRP)","award":["DM 117\/2023"],"award-info":[{"award-number":["DM 117\/2023"]}]},{"name":"Italian parent association \u201cCDKL5 insieme verso la cura\u201d","award":["PE0000006"],"award-info":[{"award-number":["PE0000006"]}]},{"name":"Italian parent association \u201cCDKL5 insieme verso la cura\u201d","award":["DN. 1553 11 October 2022"],"award-info":[{"award-number":["DN. 1553 11 October 2022"]}]},{"name":"Italian parent association \u201cCDKL5 insieme verso la cura\u201d","award":["DM 352\/2022"],"award-info":[{"award-number":["DM 352\/2022"]}]},{"name":"Italian parent association \u201cCDKL5 insieme verso la cura\u201d","award":["DM 117\/2023"],"award-info":[{"award-number":["DM 117\/2023"]}]},{"name":"Indena S.p.A.","award":["PE0000006"],"award-info":[{"award-number":["PE0000006"]}]},{"name":"Indena S.p.A.","award":["DN. 1553 11 October 2022"],"award-info":[{"award-number":["DN. 1553 11 October 2022"]}]},{"name":"Indena S.p.A.","award":["DM 352\/2022"],"award-info":[{"award-number":["DM 352\/2022"]}]},{"name":"Indena S.p.A.","award":["DM 117\/2023"],"award-info":[{"award-number":["DM 117\/2023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>CDKL5 deficiency disorder (CDD), a developmental encephalopathy caused by mutations in the cyclin-dependent kinase-like 5 (CDKL5) gene, is characterized by a complex and severe clinical picture, including early-onset epilepsy and cognitive, motor, visual, and gastrointestinal disturbances. This disease still lacks a medical treatment to mitigate, or reverse, its course and improve the patient\u2019s quality of life. Although CDD is primarily a genetic brain disorder, some evidence indicates systemic abnormalities, such as the presence of a redox imbalance in the plasma and skin fibroblasts from CDD patients and in the cardiac myocytes of a mouse model of CDD. In order to shed light on the role of oxidative stress in the CDD pathophysiology, in this study, we aimed to investigate the therapeutic potential of Coenzyme Q10 (CoQ10), which is known to be a powerful antioxidant, using in vitro and in vivo models of CDD. We found that CoQ10 supplementation not only reduces levels of reactive oxygen species (ROS) and normalizes glutathione balance but also restores the levels of markers of DNA damage (\u03b3-H2AX) and senescence (lamin B1), restoring cellular proliferation and improving cellular survival in a human neuronal model of CDD. Importantly, oral supplementation with CoQ10 exerts a protective role toward lipid peroxidation and DNA damage in the heart of a murine model of CDD, the Cdkl5 (+\/\u2212) female mouse. Our results highlight the therapeutic potential of the antioxidant supplement CoQ10 in counteracting the detrimental oxidative stress induced by CDKL5 deficiency.<\/jats:p>","DOI":"10.3390\/ijms26052204","type":"journal-article","created":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T04:10:42Z","timestamp":1740975042000},"page":"2204","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Beneficial Antioxidant Effects of Coenzyme Q10 in In Vitro and In Vivo Models of CDKL5 Deficiency Disorder"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6179-7610","authenticated-orcid":false,"given":"Manuela","family":"Loi","sequence":"first","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences, University of Bologna, Piazza di Porta San Donato 2, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7266-7352","authenticated-orcid":false,"given":"Francesca","family":"Valenti","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Biotechnology, University of Bologna, Via Irnerio 42, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Medici","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences, University of Bologna, Piazza di Porta San Donato 2, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3066-0945","authenticated-orcid":false,"given":"Nicola","family":"Mottolese","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences, University of Bologna, Piazza di Porta San Donato 2, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5029-9594","authenticated-orcid":false,"given":"Giulia","family":"Candini","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences, University of Bologna, Piazza di Porta San Donato 2, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelica Marina","family":"Bove","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences, University of Bologna, Piazza di Porta San Donato 2, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Trebbi","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences, University of Bologna, Piazza di Porta San Donato 2, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9806-2789","authenticated-orcid":false,"given":"Luca","family":"Pincigher","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Biotechnology, University of Bologna, Via Irnerio 42, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8945-6826","authenticated-orcid":false,"given":"Romana","family":"Fato","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Biotechnology, University of Bologna, Via Irnerio 42, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4387-5117","authenticated-orcid":false,"given":"Christian","family":"Bergamini","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Biotechnology, University of Bologna, Via Irnerio 42, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2623-2769","authenticated-orcid":false,"given":"Stefania","family":"Trazzi","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences, University of Bologna, Piazza di Porta San Donato 2, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3130-5168","authenticated-orcid":false,"given":"Elisabetta","family":"Ciani","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences, University of Bologna, Piazza di Porta San Donato 2, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1038\/ejhg.2012.156","article-title":"The CDKL5 disorder is an independent clinical entity associated with early-onset encephalopathy","volume":"21","author":"Fehr","year":"2013","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1111\/epi.16285","article-title":"CDKL5 deficiency disorder: Relationship between genotype, epilepsy, cortical visual impairment, and development","volume":"60","author":"Demarest","year":"2019","journal-title":"Epilepsia"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.pediatrneurol.2019.03.017","article-title":"Severity Assessment in CDKL5 Deficiency Disorder","volume":"97","author":"Demarest","year":"2019","journal-title":"Pediatr. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1111\/epi.14074","article-title":"Diagnostic outcomes for genetic testing of 70 genes in 8565 patients with epilepsy and neurodevelopmental disorders","volume":"59","author":"Lindy","year":"2018","journal-title":"Epilepsia"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2303","DOI":"10.1093\/brain\/awz195","article-title":"Incidence and phenotypes of childhood-onset genetic epilepsies: A prospective population-based national cohort","volume":"142","author":"Symonds","year":"2019","journal-title":"Brain"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.pediatrneurol.2019.02.015","article-title":"Cyclin-Dependent Kinase-Like 5 Deficiency Disorder: Clinical Review","volume":"97","author":"Olson","year":"2019","journal-title":"Pediatr. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Jakimiec, M., Paprocka, J., and Smigiel, R. (2020). CDKL5 Deficiency Disorder-A Complex Epileptic Encephalopathy. Brain Sci., 10.","DOI":"10.3390\/brainsci10020107"},{"key":"ref_8","first-page":"32048","article-title":"Functional consequences of mutations in CDKL5, an X-linked gene involved in infantile spasms and mental retardation","volume":"281","author":"Bertani","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"30101","DOI":"10.1074\/jbc.M804613200","article-title":"CDKL5 expression is modulated during neuronal development and its subcellular distribution is tightly regulated by the C-terminal tail","volume":"283","author":"Rusconi","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"12777","DOI":"10.1523\/JNEUROSCI.1102-10.2010","article-title":"CDKL5, a protein associated with rett syndrome, regulates neuronal morphogenesis via Rac1 signaling","volume":"30","author":"Chen","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"21516","DOI":"10.1073\/pnas.1216988110","article-title":"Loss of CDKL5 disrupts kinome profile and event-related potentials leading to autistic-like phenotypes in mice","volume":"109","author":"Wang","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Amendola, E., Zhan, Y., Mattucci, C., Castroflorio, E., Calcagno, E., Fuchs, C., Lonetti, G., Silingardi, D., Vyssotski, A.L., and Farley, D. (2014). Mapping pathological phenotypes in a mouse model of CDKL5 disorder. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0091613"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.nbd.2015.06.018","article-title":"Inhibition of GSK3beta rescues hippocampal development and learning in a mouse model of CDKL5 disorder","volume":"82","author":"Fuchs","year":"2015","journal-title":"Neurobiol. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"9726950","DOI":"10.1155\/2018\/9726950","article-title":"Heterozygous CDKL5 Knockout Female Mice Are a Valuable Animal Model for CDKL5 Disorder","volume":"2018","author":"Fuchs","year":"2018","journal-title":"Neural. Plast"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.nbd.2017.07.002","article-title":"CDKL5 controls postsynaptic localization of GluN2B-containing NMDA receptors in the hippocampus and regulates seizure susceptibility","volume":"106","author":"Okuda","year":"2017","journal-title":"Neurobiol. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1002\/dneu.22639","article-title":"Molecular and Synaptic Bases of CDKL5 Disorder","volume":"79","author":"Zhu","year":"2019","journal-title":"Dev. Neurobiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.nbd.2014.06.006","article-title":"Loss of CDKL5 impairs survival and dendritic growth of newborn neurons by altering AKT\/GSK-3beta signaling","volume":"70","author":"Fuchs","year":"2014","journal-title":"Neurobiol. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2244","DOI":"10.1007\/s12035-020-01884-8","article-title":"Increased DNA Damage and Apoptosis in CDKL5-Deficient Neurons","volume":"57","author":"Loi","year":"2020","journal-title":"Mol. Neurobiol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Loi, M., Bastianini, S., Candini, G., Rizzardi, N., Medici, G., Papa, V., Gennaccaro, L., Mottolese, N., Tassinari, M., and Uguagliati, B. (2023). Cardiac Functional and Structural Abnormalities in a Mouse Model of CDKL5 Deficiency Disorder. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24065552"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"764","DOI":"10.14336\/AD.2020.0827","article-title":"Age-Related Cognitive and Motor Decline in a Mouse Model of CDKL5 Deficiency Disorder is Associated with Increased Neuronal Senescence and Death","volume":"12","author":"Gennaccaro","year":"2021","journal-title":"Aging Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.neuropharm.2018.10.018","article-title":"Rescue of prepulse inhibition deficit and brain mitochondrial dysfunction by pharmacological stimulation of the central serotonin receptor 7 in a mouse model of CDKL5 Deficiency Disorder","volume":"144","author":"Vigli","year":"2019","journal-title":"Neuropharmacology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1111\/jnc.15300","article-title":"In vivo magnetic resonance spectroscopy in the brain of Cdkl5 null mice reveals a metabolic profile indicative of mitochondrial dysfunctions","volume":"157","author":"Carli","year":"2021","journal-title":"J. Neurochem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.freeradbiomed.2015.05.010","article-title":"Alteration of serum lipid profile, SRB1 loss, and impaired Nrf2 activation in CDKL5 disorder","volume":"86","author":"Pecorelli","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.clinbiochem.2011.01.007","article-title":"Increased levels of 4HNE-protein plasma adducts in Rett syndrome","volume":"44","author":"Pecorelli","year":"2011","journal-title":"Clin. Biochem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"421624","DOI":"10.1155\/2015\/421624","article-title":"Cytokine Dysregulation in MECP2- and CDKL5-Related Rett Syndrome: Relationships with Aberrant Redox Homeostasis, Inflammation, and omega-3 PUFAs","volume":"2015","author":"Leoncini","year":"2015","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/s00011-016-1014-2","article-title":"Inflammatory protein response in CDKL5-Rett syndrome: Evidence of a subclinical smouldering inflammation","volume":"66","author":"Cortelazzo","year":"2017","journal-title":"Inflamm. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1007\/978-1-4614-0653-2_21","article-title":"Oxidative stress in developmental brain disorders","volume":"724","author":"Hayashi","year":"2012","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1440-1789.2008.00888.x","article-title":"Oxidative stress in developmental brain disorders","volume":"29","author":"Hayashi","year":"2009","journal-title":"Neuropathology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.freeradbiomed.2009.05.016","article-title":"Systemic oxidative stress in classic Rett syndrome","volume":"47","author":"Ciccoli","year":"2009","journal-title":"Free Radic. Biol. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.nbd.2014.04.006","article-title":"Oxidative brain damage in Mecp2-mutant murine models of Rett syndrome","volume":"68","author":"Signorini","year":"2014","journal-title":"Neurobiol. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.nbd.2012.06.007","article-title":"Oxidative burden and mitochondrial dysfunction in a mouse model of Rett syndrome","volume":"48","author":"Grosser","year":"2012","journal-title":"Neurobiol. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.neubiorev.2018.12.009","article-title":"Disturbed redox homeostasis and oxidative stress: Potential players in the developmental regression in Rett syndrome","volume":"98","author":"Muller","year":"2019","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/s11010-019-03633-5","article-title":"Effects of oral administration of common antioxidant supplements on the energy metabolism of red blood cells. Attenuation of oxidative stress-induced changes in Rett syndrome erythrocytes by CoQ10","volume":"463","author":"Ciaccio","year":"2020","journal-title":"Mol. Cell Biochem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.tcb.2015.12.007","article-title":"Understanding Ubiquinone","volume":"26","author":"Wang","year":"2016","journal-title":"Trends Cell Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1080\/07315724.2001.10719063","article-title":"Biochemical functions of coenzyme Q10","volume":"20","author":"Crane","year":"2001","journal-title":"J. Am. Coll. Nutr."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.bbamem.2003.11.012","article-title":"Metabolism and function of coenzyme Q","volume":"1660","author":"Turunen","year":"2004","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1258\/000456303321610493","article-title":"Ubiquinone: Cholesterol\u2019s reclusive cousin","volume":"40","author":"Hargreaves","year":"2003","journal-title":"Ann. Clin. Biochem."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Pastor-Maldonado, C.J., Suarez-Rivero, J.M., Povea-Cabello, S., Alvarez-Cordoba, M., Villalon-Garcia, I., Munuera-Cabeza, M., Suarez-Carrillo, A., Talaveron-Rey, M., and Sanchez-Alcazar, J.A. (2020). Coenzyme Q(10): Novel Formulations and Medical Trends. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228432"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e621","DOI":"10.1016\/j.neurobiolaging.2011.03.025","article-title":"Prolonged coenzyme Q10 treatment in Down syndrome patients: Effect on DNA oxidation","volume":"33","author":"Tiano","year":"2012","journal-title":"Neurobiol. Aging"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Cucinotta, F., Ricciardello, A., Turriziani, L., Mancini, A., Keller, R., Sacco, R., and Persico, A.M. (2022). Efficacy and Safety of Q10 Ubiquinol with Vitamins B and E in Neurodevelopmental Disorders: A Retrospective Chart Review. Front. Psychiatry, 13.","DOI":"10.3389\/fpsyt.2022.829516"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"S78","DOI":"10.1016\/j.mito.2007.03.003","article-title":"Plasma coenzyme Q10 response to oral ingestion of coenzyme Q10 formulations","volume":"7","author":"Bhagavan","year":"2007","journal-title":"Mitochondrion"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"759","DOI":"10.2174\/1567201816666190902123147","article-title":"A New Food-grade Coenzyme Q10 Formulation Improves Bioavailability: Single and Repeated Pharmacokinetic Studies in Healthy Volunteers","volume":"16","author":"Petrangolini","year":"2019","journal-title":"Curr. Drug Deliv."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Rizzardi, N., Liparulo, I., Antonelli, G., Orsini, F., Riva, A., Bergamini, C., and Fato, R. (2021). Coenzyme Q10 Phytosome Formulation Improves CoQ10 Bioavailability and Mitochondrial Functionality in Cultured Cells. Antioxidants, 10.","DOI":"10.3390\/antiox10060927"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"77","DOI":"10.23736\/S2724-5985.20.02664-1","article-title":"Efficacy of artichoke and ginger extracts with simethicone to treat gastrointestinal symptoms in endurance athletes: A pilot study","volume":"68","author":"Drobnic","year":"2022","journal-title":"Minerva Gastroenterol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.bbrc.2007.04.106","article-title":"Simple quantitative detection of mitochondrial superoxide production in live cells","volume":"358","author":"Mukhopadhyay","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1038\/emboj.2011.492","article-title":"Oxidative stress induces an ATM-independent senescence pathway through p38 MAPK-mediated lamin B1 accumulation","volume":"31","author":"Barascu","year":"2012","journal-title":"EMBO J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1101\/gad.960502","article-title":"Nuclear lamins: Building blocks of nuclear architecture","volume":"16","author":"Goldman","year":"2002","journal-title":"Genes Dev."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1111\/j.1582-4934.2008.00676.x","article-title":"Nuclear lamins: Key regulators of nuclear structure and activities","volume":"13","author":"Prokocimer","year":"2009","journal-title":"J. Cell Mol. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.3892\/ijo.2017.4091","article-title":"Luteolin induces apoptotic cell death via antioxidant activity in human colon cancer cells","volume":"51","author":"Kang","year":"2017","journal-title":"Int. J. Oncol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Rehfeldt, S.C.H., Silva, J., Alves, C., Pinteus, S., Pedrosa, R., Laufer, S., and Goettert, M.I. (2022). Neuroprotective Effect of Luteolin-7-O-Glucoside against 6-OHDA-Induced Damage in Undifferentiated and RA-Differentiated SH-SY5Y Cells. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23062914"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Naia, L., Pinho, C.M., Dentoni, G., Liu, J., Leal, N.S., Ferreira, D.M.S., Schreiner, B., Filadi, R., Fao, L., and Connolly, N.M.C. (2021). Neuronal cell-based high-throughput screen for enhancers of mitochondrial function reveals luteolin as a modulator of mitochondria-endoplasmic reticulum coupling. BMC Biol., 19.","DOI":"10.1186\/s12915-021-00979-5"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"S107","DOI":"10.3233\/JAD-161221","article-title":"The DNA Damage Response in Neurons: Die by Apoptosis or Survive in a Senescence-Like State?","volume":"60","author":"Fielder","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1126\/science.7901908","article-title":"Oxidative stress, glutamate, and neurodegenerative disorders","volume":"262","author":"Coyle","year":"1993","journal-title":"Science"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Dubois-Deruy, E., Peugnet, V., Turkieh, A., and Pinet, F. (2020). Oxidative Stress in Cardiovascular Diseases. Antioxidants, 9.","DOI":"10.3390\/antiox9090864"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1007\/s10863-014-9581-9","article-title":"Scavenging of H2O2 by mouse brain mitochondria","volume":"46","author":"Starkov","year":"2014","journal-title":"J. Bioenerg. Biomembr."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e12105","DOI":"10.15252\/emmm.202012105","article-title":"Neuron type-specific increase in lamin B1 contributes to nuclear dysfunction in Huntington\u2019s disease","volume":"13","author":"Ito","year":"2021","journal-title":"EMBO Mol. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"19017","DOI":"10.1073\/pnas.0908686106","article-title":"A perinuclear actin cap regulates nuclear shape","volume":"106","author":"Khatau","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1091\/mbc.E17-06-0410","article-title":"Chromatin histone modifications and rigidity affect nuclear morphology independent of lamins","volume":"29","author":"Stephens","year":"2018","journal-title":"Mol. Biol. Cell"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"25768","DOI":"10.1074\/jbc.M513511200","article-title":"Lamins A and C but not lamin B1 regulate nuclear mechanics","volume":"281","author":"Lammerding","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"10428","DOI":"10.1073\/pnas.0401424101","article-title":"Lamin B1 is required for mouse development and nuclear integrity","volume":"101","author":"Vergnes","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1080\/19491034.2016.1183859","article-title":"Alzheimer\u2019s disease: An acquired neurodegenerative laminopathy","volume":"7","author":"Frost","year":"2016","journal-title":"Nucleus"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/nature11557","article-title":"Progressive degeneration of human neural stem cells caused by pathogenic LRRK2","volume":"491","author":"Liu","year":"2012","journal-title":"Nature"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1038\/s43587-022-00323-8","article-title":"Age-dependent Lamin changes induce cardiac dysfunction via dysregulation of cardiac transcriptional programs","volume":"3","author":"Kirkland","year":"2023","journal-title":"Nat. Aging"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Barcelos, I.P., and Haas, R.H. (2019). CoQ10 and Aging. Biology, 8.","DOI":"10.3390\/biology8020028"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Takahashi, M., and Takahashi, K. (2019). Water-soluble CoQ10 as A Promising Anti-aging Agent for Neurological Dysfunction in Brain Mitochondria. Antioxidants, 8.","DOI":"10.3390\/antiox8030061"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"s1","DOI":"10.1016\/0098-2997(94)90008-6","article-title":"Coenzyme Q10, plasma membrane oxidase and growth control","volume":"15","author":"Crane","year":"1994","journal-title":"Mol. Aspects Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.taap.2004.04.019","article-title":"Paraquat induces oxidative stress and neuronal cell death; neuroprotection by water-soluble Coenzyme Q10","volume":"201","author":"McCarthy","year":"2004","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/S0891-5849(99)00132-X","article-title":"Coenzyme Q10 enrichment decreases oxidative DNA damage in human lymphocytes","volume":"27","author":"Tomasetti","year":"1999","journal-title":"Free Radic. Biol. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.nut.2018.05.020","article-title":"Bioavailability of coenzyme Q10 supplements depends on carrier lipids and solubilization","volume":"57","author":"Navas","year":"2019","journal-title":"Nutrition"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"8892","DOI":"10.1073\/pnas.95.15.8892","article-title":"Coenzyme Q10 administration increases brain mitochondrial concentrations and exerts neuroprotective effects","volume":"95","author":"Matthews","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/j.freeradbiomed.2005.08.037","article-title":"Effect of coenzyme Q10 intake on endogenous coenzyme Q content, mitochondrial electron transport chain, antioxidative defenses, and life span of mice","volume":"40","author":"Sohal","year":"2006","journal-title":"Free Radic. Biol. Med."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Rabanal-Ruiz, Y., Llanos-Gonzalez, E., and Alcain, F.J. (2021). The Use of Coenzyme Q10 in Cardiovascular Diseases. Antioxidants, 10.","DOI":"10.3390\/antiox10050755"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Pallotti, F., Bergamini, C., Lamperti, C., and Fato, R. (2021). The Roles of Coenzyme Q in Disease: Direct and Indirect Involvement in Cellular Functions. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23010128"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1073\/pnas.88.5.1646","article-title":"Ubiquinol-10 protects human low density lipoprotein more efficiently against lipid peroxidation than does alpha-tocopherol","volume":"88","author":"Stocker","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Takahashi, T., Mine, Y., and Okamoto, T. (2019). Extracellular coenzyme Q(10) (CoQ(10)) is reduced to ubiquinol-10 by intact Hep G2 cells independent of intracellular CoQ(10) reduction. Arch. Biochem. Biophys., 672.","DOI":"10.1016\/j.abb.2019.108067"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"111521","DOI":"10.1016\/j.mad.2021.111521","article-title":"Coenzyme Q(10) supplementation\u2014In ageing and disease","volume":"197","author":"Aaseth","year":"2021","journal-title":"Mech. Ageing Dev."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.bbabio.2008.11.003","article-title":"Differential effects of mitochondrial Complex I inhibitors on production of reactive oxygen species","volume":"1787","author":"Fato","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1111\/febs.15561","article-title":"Coenzyme Q biosynthesis inhibition induces HIF-1alpha stabilization and metabolic switch toward glycolysis","volume":"288","author":"Liparulo","year":"2021","journal-title":"FEBS J."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Davis, B.M., Salinas-Navarro, M., Cordeiro, M.F., Moons, L., and De Groef, L. (2017). Characterizing microglia activation: A spatial statistics approach to maximize information extraction. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-01747-8"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e13521","DOI":"10.1111\/acel.13521","article-title":"Loss of lamin-B1 and defective nuclear morphology are hallmarks of astrocyte senescence in vitro and in the aging human hippocampus","volume":"21","author":"Matias","year":"2022","journal-title":"Aging Cell"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Diquigiovanni, C., Rizzardi, N., Kampmeier, A., Liparulo, I., Bianco, F., De Nicolo, B., Cataldi-Stagetti, E., Cuna, E., Severi, G., and Seri, M. (2023). Mutant SPART causes defects in mitochondrial protein import and bioenergetics reversed by Coenzyme Q. Open Biol., 13.","DOI":"10.1098\/rsob.230040"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1886","DOI":"10.1007\/s13311-022-01295-8","article-title":"Expression of a Secretable, Cell-Penetrating CDKL5 Protein Enhances the Efficacy of Gene Therapy for CDKL5 Deficiency Disorder","volume":"19","author":"Medici","year":"2022","journal-title":"Neurotherapeutics"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/S0076-6879(84)05020-5","article-title":"Simultaneous determination of reduced and oxidized ubiquinones","volume":"105","author":"Takada","year":"1984","journal-title":"Methods Enzymol."},{"key":"ref_84","first-page":"4","article-title":"Measurement of lipid peroxidation","volume":"2","author":"Reilly","year":"2001","journal-title":"Curr. Protoc. Toxicol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding","volume":"72","author":"Bradford","year":"1976","journal-title":"Anal. Biochem."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1001\/archneur.57.9.1265","article-title":"Antioxidant therapy in neurologic disease","volume":"57","author":"Delanty","year":"2000","journal-title":"Arch. Neurol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/5\/2204\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:45:07Z","timestamp":1760028307000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/5\/2204"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,28]]},"references-count":86,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["ijms26052204"],"URL":"https:\/\/doi.org\/10.3390\/ijms26052204","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,28]]}}}