{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:48:27Z","timestamp":1791416907247,"version":"4.3.3"},"reference-count":66,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2023,12,5]],"date-time":"2023-12-05T00:00:00Z","timestamp":1701734400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NICHD HD036071"},{"name":"the Intellectual and Developmental Disability Research Center grant from NICHD P50 HD103526"},{"name":"Phillips Foundation"},{"name":"Vic LaFave Sr Foundation"},{"name":"Tides Foundation"},{"name":"Intramural Research Program of the National Institute on Aging, NIH"},{"name":"Nutrimax"},{"name":"NIH (R21NS128751 to CG)"},{"name":"discretionary funds (CG)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Fragile X (FMR1) premutation is a common mutation that affects about 1 in 200 females and 1 in 450 males and can lead to the development of fragile-X-associated tremor\/ataxia syndrome (FXTAS). Although there is no targeted, proven treatment for FXTAS, research suggests that sulforaphane, an antioxidant present in cruciferous vegetables, can enhance mitochondrial function and maintain redox balance in the dermal fibroblasts of individuals with FXTAS, potentially leading to improved cognitive function. In a 24-week open-label trial involving 15 adults aged 60\u201388 with FXTAS, 11 participants successfully completed the study, demonstrating the safety and tolerability of sulforaphane. Clinical outcomes and biomarkers were measured to elucidate the effects of sulforaphane. While there were nominal improvements in multiple clinical measures, they were not significantly different after correction for multiple comparisons. PBMC energetic measures showed that the level of citrate synthase was higher after sulforaphane treatment, resulting in lower ATP production. The ratio of complex I to complex II showed positive correlations with the MoCA and BDS scores. Several mitochondrial biomarkers showed increased activity and quantity and were correlated with clinical improvements.<\/jats:p>","DOI":"10.3390\/cells12242773","type":"journal-article","created":{"date-parts":[[2023,12,5]],"date-time":"2023-12-05T11:27:06Z","timestamp":1701775626000},"page":"2773","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Open-Label Sulforaphane Trial in FMR1 Premutation Carriers with Fragile-X-Associated Tremor and Ataxia Syndrome (FXTAS)"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6301-7262","authenticated-orcid":false,"given":"Ellery","family":"Santos","sequence":"first","affiliation":[{"name":"Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, University of California Davis Health, Sacramento, CA 95817, USA"},{"name":"Department of Pediatrics, School of Medicine, University of California, Davis, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney","family":"Clark","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, School of Medicine, University of California, Davis, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hazel Maridith B.","family":"Biag","sequence":"additional","affiliation":[{"name":"Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, University of California Davis Health, Sacramento, CA 95817, USA"},{"name":"Department of Pediatrics, School of Medicine, University of California, Davis, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5136-7353","authenticated-orcid":false,"given":"Si Jie","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, School of Medicine, University of California, Davis, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoungmi","family":"Kim","sequence":"additional","affiliation":[{"name":"Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, University of California Davis Health, Sacramento, CA 95817, USA"},{"name":"Division of Biostatistics, Department of Public Health Sciences, University of California, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7758-8688","authenticated-orcid":false,"given":"Matthew D.","family":"Ponzini","sequence":"additional","affiliation":[{"name":"Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, University of California Davis Health, Sacramento, CA 95817, USA"},{"name":"Division of Biostatistics, Department of Public Health Sciences, University of California, Davis, CA 95616, 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7293-2315","authenticated-orcid":false,"given":"Federica Alice Maria","family":"Montanaro","sequence":"additional","affiliation":[{"name":"Child and Adolescent Neuropsychiatry Unit, Department of Neuroscience, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"},{"name":"Department of Education, Psychology, Communication, University of Bari Aldo Moro, 70121 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesse Tran-Emilia","family":"Gipe","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacquelyn","family":"Dayton","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA 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Modeling Fragile X Syndrome, Springer. Results and Problems in Cell Differentiation."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1038\/s10038-017-0407-6","article-title":"Genetic cluster of fragile X syndrome in a Colombian district","volume":"63","author":"Saldarriaga","year":"2018","journal-title":"J. Hum. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1212\/WNL.57.1.127","article-title":"Intention tremor, parkinsonism, and generalized brain atrophy in male carriers of fragile X","volume":"57","author":"Hagerman","year":"2001","journal-title":"Neurology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1086\/374321","article-title":"Fragile X Premutation Tremor\/Ataxia Syndrome: Molecular, Clinical, and Neuroimaging Correlates","volume":"72","author":"Jacquemont","year":"2003","journal-title":"Am. J. Hum. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1038\/nrneurol.2016.82","article-title":"Fragile X-associated tremor\/ataxia syndrome\u2014Features, mechanisms and management","volume":"12","author":"Hagerman","year":"2016","journal-title":"Nat. Rev. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1001\/jama.291.4.460","article-title":"Penetrance of the Fragile X\u2013Associated Tremor\/Ataxia Syndrome in a Premutation Carrier Population","volume":"291","author":"Jacquemont","year":"2004","journal-title":"JAMA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1016\/S1474-4422(13)70125-X","article-title":"Advances in clinical and molecular understanding of the FMR1 premutation and fragile X-associated tremor\/ataxia syndrome","volume":"12","author":"Hagerman","year":"2013","journal-title":"Lancet Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1038\/ejhg.2009.51","article-title":"Penetrance of FMR1 premutation associated pathologies in fragile X syndrome families","volume":"17","author":"Madrigal","year":"2009","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1002\/mds.21252","article-title":"Progression of tremor and ataxia in male carriers of the FMR1 premutation","volume":"22","author":"Leehey","year":"2007","journal-title":"Mov. Disord. Off. J. Mov. Disord. Soc."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/scientificamericanmind0316-34","article-title":"The Carriers","volume":"27","author":"Skomorowsky","year":"2016","journal-title":"Sci. Am. Mind"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Tassone, F., and Hall, D.A. (2016). FXTAS, FXPOI, and Other Premutation Disorders, Springer.","DOI":"10.1007\/978-3-319-33898-9"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1042\/BJ20091960","article-title":"Evidence of mitochondrial dysfunction in fragile X-associated tremor\/ataxia syndrome","volume":"429","author":"Wong","year":"2010","journal-title":"Biochem. J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"548","DOI":"10.2119\/molmed.2016.00122","article-title":"Altered redox mitochondrial biology in the neurodegenerative disorder fragile X-tremor\/ataxia syndrome: Use of antioxidants in precision medicine","volume":"22","author":"Song","year":"2016","journal-title":"Mol. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"6896","DOI":"10.1007\/s12035-016-0194-7","article-title":"Impaired mitochondrial function and dynamics in the pathogenesis of FXTAS","volume":"54","author":"Madrigal","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/s41536-020-00107-x","article-title":"Mitochondrial dysfunction in neurological disorders: Exploring mitochondrial transplantation","volume":"5","author":"Norat","year":"2020","journal-title":"npj Regen. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1631\/jzus.B1900614","article-title":"Effects of sulforaphane on brain mitochondria: Mechanistic view and future directions","volume":"21","author":"Jardim","year":"2020","journal-title":"J. Zhejiang Univ.\u2013Sci. B"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Wei, J., Zhao, Q., Zhang, Y., Shi, W., Wang, H., Zheng, Z., Meng, L., Xin, Y., and Jiang, X. (2021). Sulforaphane-mediated Nrf2 activation prevents radiation-induced skin injury through inhibiting the oxidative-stress-activated DNA damage and NLRP3 inflammasome. Antioxidants, 10.","DOI":"10.3390\/antiox10111850"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"13291","DOI":"10.1074\/jbc.R900010200","article-title":"The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress","volume":"284","author":"Nguyen","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.tibs.2014.02.002","article-title":"The Nrf2 regulatory network provides an interface between redox and intermediary metabolism","volume":"39","author":"Hayes","year":"2014","journal-title":"Trends Biochem. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.redox.2016.11.007","article-title":"Sulforaphane is a Nrf2-independent inhibitor of mitochondrial fission","volume":"11","author":"Berry","year":"2017","journal-title":"Redox Biol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Napoli, E., Flores, A., Mansuri, Y., Hagerman, R.J., and Giulivi, C. (2021). Sulforaphane improves mitochondrial metabolism in fibroblasts from patients with fragile X-associated tremor and ataxia syndrome. Neurobiol. Dis., 157.","DOI":"10.1016\/j.nbd.2021.105427"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/1866-1955-6-31","article-title":"Emerging topics in FXTAS","volume":"6","author":"Hall","year":"2014","journal-title":"J. Neurodev. Disord."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"87","DOI":"10.4088\/JCP.v67n0112","article-title":"Psychiatric Phenotype of the Fragile X-Associated Tremor\/Ataxia Syndrome (FXTAS) in Males: Newly Described Fronto-Subcortical Dementia","volume":"67","author":"Bacalman","year":"2006","journal-title":"J. Clin. Psychiatry"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/j.jalz.2008.07.003","article-title":"Status of computerized cognitive testing in aging: A systematic review","volume":"4","author":"Wild","year":"2008","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1080\/13803390903042379","article-title":"Attention and working memory deficits in mild cognitive impairment","volume":"32","author":"Saunders","year":"2010","journal-title":"J. Clin. Exp. Neuropsychol."},{"key":"ref_26","unstructured":"Derogatis, L.R., and Kathryn, L. (2000). Handbook of Psychological Assessment in Primary Care Settings, Routledge."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"883","DOI":"10.2466\/pms.1992.74.3.883","article-title":"Reliabilities, norms and factor structure of the Behavioral Dyscontrol Scale","volume":"74","author":"Grigsby","year":"1992","journal-title":"Percept. Mot. Ski."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1093\/arclin\/acu022","article-title":"The Behavioral Dyscontrol Scale-II with non-elderly veterans","volume":"29","author":"Shura","year":"2014","journal-title":"Arch. Clin. Neuropsychol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1111\/j.1532-5415.2005.53221.x","article-title":"The Montreal Cognitive Assessment, MoCA: A brief screening tool for mild cognitive impairment","volume":"53","author":"Nasreddine","year":"2005","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"43","DOI":"10.2353\/jmoldx.2008.070073","article-title":"A rapid polymerase chain reaction-based screening method for identification of all expanded alleles of the fragile X (FMR1) gene in newborn and high-risk populations","volume":"10","author":"Tassone","year":"2008","journal-title":"J. Mol. Diagn."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1373\/clinchem.2009.136101","article-title":"A novel FMR1 PCR method for the routine detection of low abundance expanded alleles and full mutations in fragile X syndrome","volume":"56","author":"Sah","year":"2010","journal-title":"Clin. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1002\/(SICI)1096-8628(19990528)84:3<250::AID-AJMG17>3.0.CO;2-4","article-title":"FMRP expression as a potential prognostic indicator in fragile X syndrome","volume":"84","author":"Tassone","year":"1999","journal-title":"Am. J. Med. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1086\/302720","article-title":"Elevated levels of FMR1 mRNA in carrier males: A new mechanism of involvement in the fragile-X syndrome","volume":"66","author":"Tassone","year":"2000","journal-title":"Am. J. Hum. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Kim, K., Hessl, D., Randol, J.L., Espinal, G.M., Schneider, A., Protic, D., Aydin, E.Y., Hagerman, R.J., and Hagerman, P.J. (2019). Association between IQ and FMR1 protein (FMRP) across the spectrum of CGG repeat expansions. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0226811"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1093\/brain\/awac258","article-title":"Extracellular vesicle biomarkers for cognitive impairment in Parkinson\u2019s disease","volume":"146","author":"Blommer","year":"2023","journal-title":"Brain"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"278","DOI":"10.3389\/fnins.2017.00278","article-title":"Plasma extracellular vesicles enriched for neuronal origin: A potential window into brain pathologic processes","volume":"11","author":"Mustapic","year":"2017","journal-title":"Front. Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3334","DOI":"10.1096\/fj.201600315R","article-title":"Warburg effect linked to cognitive-executive deficits in FMR1 premutation","volume":"30","author":"Napoli","year":"2016","journal-title":"FASEB J."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Wang, J.Y., Napoli, E., Kim, K., McLennan, Y.A., Hagerman, R.J., and Giulivi, C. (2021). Brain atrophy and white matter damage linked to peripheral bioenergetic deficits in the neurodegenerative disease FXTAS. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22179171"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2389","DOI":"10.1001\/jama.2010.1706","article-title":"Mitochondrial dysfunction in autism","volume":"304","author":"Giulivi","year":"2010","journal-title":"JAMA"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"23240","DOI":"10.1074\/jbc.M115.672360","article-title":"Mitochondrial citrate transporter-dependent metabolic signature in the 22q11.2 deletion syndrome","volume":"290","author":"Napoli","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1093\/hmg\/dds503","article-title":"Defective mitochondrial disulfide relay system, altered mitochondrial morphology and function in Huntington\u2019s disease","volume":"22","author":"Napoli","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/2040-2392-4-2","article-title":"Evidence of reactive oxygen species-mediated damage to mitochondrial DNA in children with typical autism","volume":"4","author":"Napoli","year":"2013","journal-title":"Mol. Autism"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1093\/toxsci\/kfs339","article-title":"Toxicity of the flame-retardant BDE-49 on brain mitochondria and neuronal progenitor striatal cells enhanced by a PTEN-deficient background","volume":"132","author":"Napoli","year":"2013","journal-title":"Toxicol. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"609602","DOI":"10.1155\/2013\/609602","article-title":"Gestational exposure to a viral mimetic poly (i: C) results in long-lasting changes in mitochondrial function by leucocytes in the adult offspring","volume":"2013","author":"Giulivi","year":"2013","journal-title":"Mediat. Inflamm."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Napoli, E., Ross-Inta, C., Wong, S., Hung, C., Fujisawa, Y., Sakaguchi, D., Angelastro, J., Omanska-Klusek, A., Schoenfeld, R., and Giulivi, C. (2012). Mitochondrial dysfunction in Pten haplo-insufficient mice with social deficits and repetitive behavior: Interplay between Pten and p 53. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0042504"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3079","DOI":"10.1093\/hmg\/ddr211","article-title":"Altered zinc transport disrupts mitochondrial protein processing\/import in fragile X-associated tremor\/ataxia syndrome","volume":"20","author":"Napoli","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1007\/s12311-016-0779-8","article-title":"Altered bioenergetics in primary dermal fibroblasts from adult carriers of the FMR1 premutation before the onset of the neurodegenerative disease fragile X-associated tremor\/ataxia syndrome","volume":"15","author":"Napoli","year":"2016","journal-title":"Cerebellum"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Nolin, S.L., Napoli, E., Flores, A., Hagerman, R.J., and Giulivi, C. (2021). Deficits in prenatal serine biosynthesis underlie the mitochondrial dysfunction associated with the autism-linked FMR1 gene. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22115886"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1021\/tx0502138","article-title":"Identification of sensor cysteines in human Keap1 modified by the cancer chemopreventive agent sulforaphane","volume":"18","author":"Hong","year":"2005","journal-title":"Chem. Res. Toxicol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1146\/annurev-pharmtox-011112-140320","article-title":"Role of nrf2 in oxidative stress and toxicity","volume":"53","author":"Ma","year":"2013","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"14130","DOI":"10.1038\/s41598-017-14520-8","article-title":"Sulforaphane reactivates cellular antioxidant defense by inducing Nrf2\/ARE\/Prdx6 activity during aging and oxidative stress","volume":"7","author":"Kubo","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s13229-021-00447-5","article-title":"Randomized controlled trial of sulforaphane and metabolite discovery in children with Autism Spectrum Disorder","volume":"12","author":"Zimmerman","year":"2021","journal-title":"Mol. Autism"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Gwon, Y., Oh, J., and Kim, J.-S. (2020). Sulforaphane induces colorectal cancer cell proliferation through Nrf2 activation in a p53-dependent manner. Appl. Biol. Chem., 63.","DOI":"10.1186\/s13765-020-00578-y"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"135624","DOI":"10.1016\/j.scitotenv.2019.135624","article-title":"Emerging promise of sulforaphane-mediated Nrf2 signaling cascade against neurological disorders","volume":"707","author":"Uddin","year":"2020","journal-title":"Sci. Total Environ."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"5440","DOI":"10.1002\/ptr.7176","article-title":"Sulforaphane: A review of its therapeutic potentials, advances in its nanodelivery, recent patents, and clinical trials","volume":"35","author":"Mangla","year":"2021","journal-title":"Phytother. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"129","DOI":"10.31486\/toj.21.0084","article-title":"Rates of Cognitive Decline in 100 Patients with Alzheimer Disease","volume":"22","author":"Feehan","year":"2022","journal-title":"Ochsner J."},{"key":"ref_57","first-page":"100008","article-title":"Longitudinal changes in MoCA performances in patients with mild cognitive impairment and small vessel disease. Results from the VMCI-Tuscany Study","volume":"2","author":"Salvadori","year":"2021","journal-title":"Cereb. Circ.\u2013Cogn. Behav."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.gde.2006.04.010","article-title":"Transcription, translation and fragile X syndrome","volume":"16","author":"Garber","year":"2006","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Villavicencio Tejo, F., and Quintanilla, R.A. (2021). Contribution of the Nrf2 pathway on oxidative damage and mitochondrial failure in Parkinson and Alzheimer\u2019s disease. Antioxidants, 10.","DOI":"10.3390\/antiox10071069"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Lasbleiz, C., Peyrel, A., Tarot, P., Sarniguet, J., Crouzier, L., Cubedo, N., Delprat, B., Rossel, M., Maurice, T., and Li\u00e9vens, J.-C. (2022). Sigma-1 receptor agonist PRE-084 confers protection against TAR DNA-binding protein-43 toxicity through NRF2 signalling. Redox Biol., 58.","DOI":"10.1016\/j.redox.2022.102542"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Shimizu, S., Kasai, S., Yamazaki, H., Tatara, Y., Mimura, J., Engler, M.J., Tanji, K., Nikaido, Y., Inoue, T., and Suganuma, H. (2022). Sulforaphane increase mitochondrial biogenesis-related gene expression in the hippocampus and suppresses age-related cognitive decline in mice. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23158433"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e13261","DOI":"10.1111\/acel.13261","article-title":"Sulforaphane prevents age-associated cardiac and muscular dysfunction through Nrf2 signaling","volume":"19","author":"Bose","year":"2020","journal-title":"Aging Cell"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s13229-018-0218-4","article-title":"Identification of urinary metabolites that correlate with clinical improvements in children with autism treated with sulforaphane from broccoli","volume":"9","author":"Bent","year":"2018","journal-title":"Mol. Autism"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Shekarri, Q., and Dekker, M. (2021). A physiological-based model for simulating the bioavailability and kinetics of sulforaphane from broccoli products. Foods, 10.","DOI":"10.3390\/foods10112761"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Schepici, G., Bramanti, P., and Mazzon, E. (2020). Efficacy of sulforaphane in neurodegenerative diseases. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228637"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1002\/ana.25934","article-title":"Safety and efficacy of omaveloxolone in Friedreich ataxia (MOXIe study)","volume":"89","author":"Lynch","year":"2021","journal-title":"Ann. Neurol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/24\/2773\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:33:41Z","timestamp":1760132021000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/24\/2773"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,5]]},"references-count":66,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["cells12242773"],"URL":"https:\/\/doi.org\/10.3390\/cells12242773","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,5]]}}}