{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T00:52:38Z","timestamp":1792284758660,"version":"4.4.0"},"reference-count":95,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Riboflavin (vitamin B2), a precursor of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), is essential for mitochondrial function, redox balance, and neuronal viability. Impairments in riboflavin transport and metabolism contribute to a growing spectrum of neurological diseases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>This review provides a comprehensive update on the therapeutic applications, metabolic mechanisms, and gene-based strategies involving riboflavin in neurological disorders.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We systematically analyzed clinical and experimental studies published between 2012 and 2025, focusing on riboflavin-responsive conditions and molecular mechanisms relevant to neurological pathology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Riboflavin supplementation\u2014particularly in high doses\u2014has demonstrated substantial efficacy in conditions such as riboflavin transporter deficiency (RTD), multiple acyl-CoA dehydrogenase deficiency (MADD), and migraine. Emerging data suggest potential benefit in Parkinson\u2019s disease, Alzheimer\u2019s disease, multiple sclerosis, and acute brain injury. Mechanistically, riboflavin supports mitochondrial bioenergetics, antioxidant systems, and epigenetic regulation. Recent advances in gene therapy and pharmacological chaperones targeting riboflavin-dependent pathways offer promising therapeutic directions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Riboflavin is evolving from a conventional micronutrient into a multifaceted therapeutic agent in neurology. Integration of gene-based approaches, targeted delivery systems, and biomarker-guided interventions may establish riboflavin as a key component of precision medicine strategies for neurological disorders.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2025.1663136","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T04:10:59Z","timestamp":1756786259000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Riboflavin in neurological diseases: therapeutic advances, metabolic insights, and emerging genetic strategies"],"prefix":"10.3389","volume":"16","author":[{"given":"Zhiming","family":"Tao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinglu","family":"Huo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaosheng","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianmin","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,2]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"973","DOI":"10.3945\/an.116.012716","article-title":"Riboflavin","volume":"7","author":"Pinto","year":"2016","journal-title":"Adv Nutr"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"68","DOI":"10.3390\/nu8020068","article-title":"B vitamins and the brain: mechanisms, dose and efficacy\u2014a review","volume":"8","author":"Kennedy","year":"2016","journal-title":"Nutrients"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1007\/s40261-021-01038-1","article-title":"Riboflavin in neurological diseases: a narrative review","volume":"41","author":"Plantone","year":"2021","journal-title":"Clin Drug Investig"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1007\/s10545-010-9242-z","article-title":"Brown\u2013Vialetto\u2013Van Laere and Fazio Londe syndrome is associated with a riboflavin transporter defect mimicking mild MADD: a new inborn error of metabolism with potential treatment","volume":"34","author":"Bosch","year":"2011","journal-title":"J Inherit Metab Dis"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"52","DOI":"10.3390\/jcm6050052","article-title":"Riboflavin responsive mitochondrial dysfunction in neurodegenerative diseases","volume":"6","author":"Udhayabanu","year":"2017","journal-title":"J Clin Med"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"333","DOI":"10.3389\/fneur.2017.00333","article-title":"Riboflavin has neuroprotective potential: focus on Parkinson\u2019s disease and migraine","volume":"8","author":"Marashly","year":"2017","journal-title":"Front Neurol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1409","DOI":"10.1590\/S0100-879X2003001000019","article-title":"High doses of riboflavin and the elimination of dietary red meat promote the recovery of some motor functions in Parkinson\u2019s disease patients","volume":"36","author":"Coimbra","year":"2003","journal-title":"Braz J Med Biol Res"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1080\/1028415X.2023.2288387","article-title":"Effects of riboflavin in the treatment of brain damage caused by oxygen deprivation: an integrative systematic review","volume":"27","author":"Silva-Araujo","year":"2024","journal-title":"Nutr Neurosci"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"108023","DOI":"10.1016\/j.pharmthera.2021.108023","article-title":"Recent advances in riboflavin transporter RFVT and its genetic disease","volume":"233","author":"Jin","year":"2022","journal-title":"Pharmacol Ther"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"e2300180","DOI":"10.1002\/advs.202300180","article-title":"Biomimetic remodeling of microglial riboflavin metabolism ameliorates cognitive impairment by modulating neuroinflammation","volume":"10","author":"Zhang","year":"2023","journal-title":"Adv Sci"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1038\/s10038-023-01216-3","article-title":"A comparative study on riboflavin responsive multiple acyl-CoA dehydrogenation deficiency due to variants in FLAD1 and ETFDH gene","volume":"69","author":"Wen","year":"2024","journal-title":"J Hum Genet"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1007\/s10545-016-9924-2","article-title":"Clinical presentation and outcome of riboflavin transporter deficiency: mini review after five years of experience","volume":"39","author":"Jaeger","year":"2016","journal-title":"J Inherit Metab Dis"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"27557","DOI":"10.1038\/srep27557","article-title":"Disruption of Slc52a3 gene causes neonatal lethality with riboflavin deficiency in mice","volume":"6","author":"Yoshimatsu","year":"2016","journal-title":"Sci Rep"},{"key":"ref14","article-title":"Riboflavin transporter deficiency","volume-title":"GeneReviews","author":"Ricci","year":"2014"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"471","DOI":"10.4103\/JPN.JPN_131_17","article-title":"Riboflavin treatment in genetically proven Brown\u2013Vialetto\u2013Van Laere syndrome","volume":"13","author":"Garg","year":"2018","journal-title":"J Pediatr Neurosci"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1136\/practneurol-2016-001488","article-title":"Remarkable motor recovery after riboflavin therapy in adult-onset Brown\u2013Vialetto\u2013Van Laere syndrome","volume":"17","author":"Bashford","year":"2017","journal-title":"Pract Neurol"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1093\/hmg\/ddae171","article-title":"Development of a riboflavin-responsive model of riboflavin transporter deficiency in zebrafish","volume":"34","author":"Choueiri","year":"2025","journal-title":"Hum Mol Genet"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"18443","DOI":"10.1038\/s41598-020-75601-9","article-title":"Effect of riboflavin deficiency on development of the cerebral cortex in Slc52a3 knockout mice","volume":"10","author":"Jin","year":"2020","journal-title":"Sci Rep"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1523773","DOI":"10.3389\/fncel.2025.1523773","article-title":"Riboflavin transporter deficiency: AAV9-SLC52A2 gene therapy as a new therapeutic strategy","volume":"19","author":"Mei","year":"2025","journal-title":"Front Cell Neurosci"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1111\/dmcn.16083","article-title":"Long-term outcomes in children with riboflavin transporter deficiency and surveillance recommendations","volume":"67","author":"Fennessy","year":"2025","journal-title":"Dev Med Child Neurol"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1016\/j.nmd.2009.01.008","article-title":"ETFDH mutations, CoQ10 levels, and respiratory chain activities in patients with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency","volume":"19","author":"Liang","year":"2009","journal-title":"Neuromuscul Disord"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"25374","DOI":"10.1038\/s41598-024-75286-4","article-title":"ETFDH mutation involves excessive apoptosis and neurite outgrowth defect via Bcl2 pathway","volume":"14","author":"Lin","year":"2024","journal-title":"Sci Rep"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"290","DOI":"10.4274\/balkanmedj.galenos.2022.2022-1-127","article-title":"Characterization of 31 patients with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency","volume":"39","author":"Zhang","year":"2022","journal-title":"Balkan Med J"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"19418744251324959","DOI":"10.1177\/19418744251324959","article-title":"Late-onset multiple acyl-CoA dehydrogenase deficiency presenting as hyperammonemia and encephalopathy: case series","author":"Viguera Altolaguirre","year":"2025","journal-title":"Neurohospitalist"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"105369","DOI":"10.1016\/j.nmd.2025.105369","article-title":"Late-onset multiple-acyl-CoA-dehydrogenase deficiency-like condition: the Northern Ireland experience","volume":"51","author":"McCarron","year":"2025","journal-title":"Neuromuscul Disord"},{"key":"ref26","article-title":"Multiple acyl-CoA dehydrogenase deficiency","volume-title":"GeneReviews","author":"Prasun","year":"2020"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"432","DOI":"10.3390\/metabo15070432","article-title":"Management of multiple Acyl-CoA dehydrogenase deficiency (MADD) in pregnancy","volume":"15","author":"Shear","year":"2025","journal-title":"Metabolites"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"2612","DOI":"10.3390\/nu13082612","article-title":"Experimental and clinical evidence of the effectiveness of riboflavin on migraines","volume":"13","author":"Yamanaka","year":"2021","journal-title":"Nutrients"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1212\/WNL.50.2.466","article-title":"Effectiveness of high-dose riboflavin in migraine prophylaxis. A randomized controlled trial","volume":"50","author":"Schoenen","year":"1998","journal-title":"Neurology"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"e2438666","DOI":"10.1001\/jamanetworkopen.2024.38666","article-title":"Preventive medications in pediatric migraine: a network meta-analysis","volume":"7","author":"Kohandel Gargari","year":"2024","journal-title":"JAMA Netw Open"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1097\/WNO.0000000000000841","article-title":"Complementary and integrative health treatments for migraine","volume":"39","author":"Patel","year":"2019","journal-title":"J Neuroophthalmol"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"1561000","DOI":"10.3389\/fneur.2025.1561000","article-title":"Energy metabolism disorders in migraine: triggers, pathways, and therapeutic repurposing","volume":"16","author":"Sun","year":"2025","journal-title":"Front Neurol"},{"key":"ref33","article-title":"Study suggests 2 vitamin B deficiencies may play role in Parkinson\u2019s disease2024","author":"Marcin","year":"2024"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"68","DOI":"10.3389\/fneur.2011.00068","article-title":"The promise of neuroprotective agents in Parkinson's disease","volume":"2","author":"Seidl","year":"2011","journal-title":"Front Neurol"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1038\/s41531-024-00724-z","article-title":"Meta-analysis of shotgun sequencing of gut microbiota in Parkinson\u2019s disease","volume":"10","author":"Nishiwaki","year":"2024","journal-title":"npj Parkinsons Dis"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.4314\/tjpr.v17i6.10","article-title":"Vitamin B2 blocks development of Alzheimer\u2019s disease in APP\/PS1 transgenic mice via anti-oxidative mechanism","volume":"17","author":"Zhao","year":"2018","journal-title":"Trop J Pharm Res"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"226","DOI":"10.3389\/fnagi.2019.00226","article-title":"Dietary intake of riboflavin and unsaturated fatty acid can improve the multi-domain cognitive function in middle-aged and elderly populations: a 2-year prospective cohort study","volume":"11","author":"Tao","year":"2019","journal-title":"Front Aging Neurosci"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"9523","DOI":"10.1073\/pnas.1301816110","article-title":"Preventing Alzheimer\u2019s disease-related gray matter atrophy by B-vitamin treatment","volume":"110","author":"Douaud","year":"2013","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref39","first-page":"439","article-title":"Brain-derived neurotrophic and immunologic factors: beneficial effects of riboflavin on motor disability in murine model of multiple sclerosis","volume":"19","author":"Naghashpour","year":"2016","journal-title":"Iran J Basic Med Sci"},{"key":"ref40","article-title":"Riboflavin (vitamin B2)\u2014micronutrient information center","year":"2023"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"37","DOI":"10.17116\/jnevro201811810137","article-title":"Cytoflavin in the complex therapy of multiple sclerosis","volume":"118","author":"Karpov","year":"2018","journal-title":"Zh Nevrol Psikhiatr Im S S Korsakova"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.3390\/children10061022","article-title":"Multiple sclerosis-related dietary and nutritional issues: an updated scoping review with a focus on pediatrics","volume":"10","author":"Mandato","year":"2023","journal-title":"Children"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.ejpn.2008.01.003","article-title":"Riboflavin treatment in a case with l-2-hydroxyglutaric aciduria","volume":"13","author":"Yilmaz","year":"2009","journal-title":"Eur J Paediatr Neurol"},{"key":"ref44","doi-asserted-by":"publisher","DOI":"10.1007\/s13353-025-00974-4","article-title":"Riboflavin treatment in L-2-hydroxyglutaric aciduria: report on a pediatric patient and literature review","author":"Lipinski","year":"2025","journal-title":"J Appl Genet"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"100979","DOI":"10.1016\/j.ymgmr.2023.100979","article-title":"Glutaric aciduria and L-2-hydroxyglutaric aciduria: clinical and molecular findings of 35 patients from Turkey","volume":"36","author":"Bozaci","year":"2023","journal-title":"Mol Genet Metab Rep"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"e8872","DOI":"10.1371\/journal.pone.0008872","article-title":"Flavin adenine dinucleotide rescues the phenotype of frataxin deficiency","volume":"5","author":"Gonzalez-Cabo","year":"2010","journal-title":"PLoS One"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"1972","DOI":"10.1096\/fj.03-0240fje","article-title":"Mitochondria-targeted antioxidants protect Friedreich ataxia fibroblasts from endogenous oxidative stress more effectively than untargeted antioxidants","volume":"17","author":"Jauslin","year":"2003","journal-title":"FASEB J"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"664","DOI":"10.3390\/antiox9080664","article-title":"Antioxidant therapies and oxidative stress in Friedreich\u2019s ataxia: the right path or just a diversion?","volume":"9","author":"Rodr\u00edguez","year":"2020","journal-title":"Antioxidants"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1111\/ane.12141","article-title":"Triple therapy with deferiprone, idebenone and riboflavin in Friedreich\u2019s ataxia\u2014open-label trial","volume":"129","author":"Arpa","year":"2014","journal-title":"Acta Neurol Scand"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1007\/s12311-013-0482-y","article-title":"Triple therapy with darbepoetin alfa, idebenone, and riboflavin in Friedreich\u2019s ataxia: an open-label trial","volume":"12","author":"Arpa","year":"2013","journal-title":"Cerebellum"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1007\/s40263-024-01113-z","article-title":"New and emerging drug and gene therapies for Friedreich ataxia","volume":"38","author":"Scott","year":"2024","journal-title":"CNS Drugs"},{"key":"ref52","article-title":"LX2006 gene therapy - drug development pipeline","year":"2023"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1007\/s12017-023-08750-5","article-title":"A missense variant in AIFM1 caused mitochondrial dysfunction and intolerance to riboflavin deficiency","volume":"25","author":"Zhao","year":"2023","journal-title":"NeuroMolecular Med"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.ejpn.2017.09.004","article-title":"Mutations in AIFM1 cause an X-linked childhood cerebellar ataxia partially responsive to riboflavin","volume":"22","author":"Heimer","year":"2018","journal-title":"Eur J Paediatr Neurol"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"3808","DOI":"10.1212\/WNL.0000000000211252","article-title":"Riboflavin responsive slowly progressive early onset motor neuron disease caused by a novel mutation in AIFM1 (P2-11.034)","volume":"104","author":"Durmus","year":"2025","journal-title":"Neurology"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"1588","DOI":"10.24976\/Discov.Med.202436187.145","article-title":"The effect of riboflavin on neurological rehabilitation after traumatic brain injury in children","volume":"36","author":"Cai","year":"2024","journal-title":"Discov Med"},{"key":"ref57","doi-asserted-by":"publisher","first-page":"1237","DOI":"10.1038\/sj.ejcn.1602666","article-title":"Riboflavin status in acute ischaemic stroke","volume":"61","author":"Gariballa","year":"2007","journal-title":"Eur J Clin Nutr"},{"key":"ref58","doi-asserted-by":"publisher","first-page":"3847","DOI":"10.3390\/ijms21113847","article-title":"Riboflavin deficiency\u2014implications for general human health and inborn errors of metabolism","volume":"21","author":"Mosegaard","year":"2020","journal-title":"Int J Mol Sci"},{"key":"ref59","doi-asserted-by":"publisher","first-page":"5310","DOI":"10.3390\/ijms21155310","article-title":"Development of novel experimental models to study flavoproteome alterations in human neuromuscular diseases: the effect of RF therapy","volume":"21","author":"Tolomeo","year":"2020","journal-title":"Int J Mol Sci"},{"key":"ref60","doi-asserted-by":"publisher","first-page":"1130","DOI":"10.1016\/j.ajhg.2016.04.006","article-title":"Riboflavin-responsive and -non-responsive mutations in FAD synthase cause multiple acyl-CoA dehydrogenase and combined respiratory-chain deficiency","volume":"98","author":"Olsen","year":"2016","journal-title":"Am J Hum Genet"},{"key":"ref61","doi-asserted-by":"publisher","first-page":"105470","DOI":"10.1016\/j.jbc.2023.105470","article-title":"Complex II ambiguities-FADH2 in the electron transfer system","volume":"300","author":"Gnaiger","year":"2024","journal-title":"J Biol Chem"},{"key":"ref62","doi-asserted-by":"publisher","first-page":"1612","DOI":"10.3390\/cells12121612","article-title":"Modulation of glial cell functions by the gut-brain Axis: a role in neurodegenerative disorders and pain transmission","volume":"12","author":"Magni","year":"2023","journal-title":"Cells"},{"key":"ref63","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1038\/s41392-023-01486-5","article-title":"Role of neuroinflammation in neurodegeneration development","volume":"8","author":"Zhang","year":"2023","journal-title":"Signal Transduct Target Ther"},{"key":"ref64","doi-asserted-by":"publisher","first-page":"3024","DOI":"10.1111\/bph.16184","article-title":"Riboflavin protects against heart failure via SCAD-dependent DJ-1-Keap1-Nrf2 signalling pathway","volume":"180","author":"Xu","year":"2023","journal-title":"Br J Pharmacol"},{"key":"ref65","doi-asserted-by":"publisher","first-page":"1887","DOI":"10.1017\/S0007114521005031","article-title":"Riboflavin is an antioxidant: a review update","volume":"128","author":"Olfat","year":"2022","journal-title":"Br J Nutr"},{"key":"ref66","doi-asserted-by":"publisher","first-page":"1969","DOI":"10.1038\/s41467-022-29552-6","article-title":"Microglial NF-kappaB drives tau spreading and toxicity in a mouse model of tauopathy","volume":"13","author":"Wang","year":"2022","journal-title":"Nat Commun"},{"key":"ref67","doi-asserted-by":"publisher","first-page":"1231706","DOI":"10.3389\/fragi.2023.1231706","article-title":"The dual face of microglia (M1\/M2) as a potential target in the protective effect of nutraceuticals against neurodegenerative diseases","volume":"4","author":"Darwish","year":"2023","journal-title":"Front Aging"},{"key":"ref68","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1186\/1742-2094-11-98","article-title":"Neuroinflammation and M2 microglia: the good, the bad, and the inflamed","volume":"11","author":"Cherry","year":"2014","journal-title":"J Neuroinflammation"},{"key":"ref69","doi-asserted-by":"publisher","first-page":"3353","DOI":"10.1007\/s00018-018-2864-2","article-title":"Crosstalk between metabolism and epigenetic modifications in autoimmune diseases: a comprehensive overview","volume":"75","author":"Wang","year":"2018","journal-title":"Cell Mol Life Sci"},{"key":"ref70","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1038\/jhg.2014.10","article-title":"Riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency in 13 cases, and a literature review in mainland Chinese patients","volume":"59","author":"Zhu","year":"2014","journal-title":"J Hum Genet"},{"key":"ref71","doi-asserted-by":"publisher","first-page":"a006081","DOI":"10.1101\/mcs.a006081","article-title":"Severe multisystem pathology, metabolic acidosis, mitochondrial dysfunction, and early death associated with an X-linked AIFM1 variant","volume":"7","author":"Moss","year":"2021","journal-title":"Cold Spring Harb Mol Case Stud"},{"key":"ref72","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1097\/HEP.0000000000000578","article-title":"Emerging and potential use of CRISPR in human liver disease","volume":"82","author":"Adlat","year":"2025","journal-title":"Hepatology"},{"key":"ref73","doi-asserted-by":"publisher","first-page":"106982","DOI":"10.1016\/j.ymgme.2022.106982","article-title":"Synthetic mRNA rescues very long-chain acyl-CoA dehydrogenase deficiency in patient fibroblasts and a murine model","volume":"138","author":"Zhao","year":"2023","journal-title":"Mol Genet Metab"},{"key":"ref74","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.1007\/s00439-016-1691-5","article-title":"Gene correction in patient-specific iPSCs for therapy development and disease modeling","volume":"135","author":"Jang","year":"2016","journal-title":"Hum Genet"},{"key":"ref75","doi-asserted-by":"publisher","first-page":"e200216","DOI":"10.1212\/NXG.0000000000200216","article-title":"Novel AIFM1 variant in 2 siblings with sensorineural hearing loss and cerebellar ataxia","volume":"10","author":"Vasquez","year":"2024","journal-title":"Neurol Genet"},{"key":"ref76","doi-asserted-by":"publisher","first-page":"103413","DOI":"10.1016\/j.redox.2024.103413","article-title":"Riboflavin kinase binds and activates inducible nitric oxide synthase to reprogram macrophage polarization","volume":"78","author":"Shan","year":"2024","journal-title":"Redox Biol"},{"key":"ref77","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1002\/jmd2.12024","article-title":"Impaired fat oxidation during exercise in multiple acyl-CoA dehydrogenase deficiency","volume":"46","author":"Madsen","year":"2019","journal-title":"JIMD Rep"},{"key":"ref78","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1007\/BF00445792","article-title":"Glutaric aciduria type II: treatment with riboflavine, carnitine and insulin","volume":"143","author":"Mooy","year":"1984","journal-title":"Eur J Pediatr"},{"key":"ref79","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.expneurol.2009.04.001","article-title":"Alpha-lipoic acid and frataxin: a new indication for an old antioxidant?","volume":"218","author":"Russell","year":"2009","journal-title":"Exp Neurol"},{"key":"ref80","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.trsl.2020.08.009","article-title":"Friedreich ataxia: current state-of-the-art, and future prospects for mitochondrial-focused therapies","volume":"229","author":"Pallardo","year":"2021","journal-title":"Transl Res"},{"key":"ref81","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1212\/01.WNL.0000151975.03598.ED","article-title":"Efficacy of coenzyme Q10 in migraine prophylaxis: a randomized controlled trial","volume":"64","author":"Sandor","year":"2005","journal-title":"Neurology"},{"key":"ref82","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1186\/s10194-015-0516-6","article-title":"Improvement of migraine symptoms with a proprietary supplement containing riboflavin, magnesium and Q10: a randomized, placebo-controlled, double-blind, multicenter trial","volume":"16","author":"Gaul","year":"2015","journal-title":"J Headache Pain"},{"key":"ref83","article-title":"Incorporating nutraceuticals for migraine prevention","year":"2021"},{"key":"ref84","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2019\/9426867","article-title":"Benefits of vitamins in the treatment of Parkinson\u2019s disease","volume":"2019","author":"Zhao","year":"2019","journal-title":"Oxid Med Cell Longev"},{"key":"ref85","doi-asserted-by":"publisher","first-page":"1557","DOI":"10.1212\/WNL.31.12.1557","article-title":"Riboflavin-responsive lipid myopathy and carnitine deficiency","volume":"31","author":"Carroll","year":"1981","journal-title":"Neurology"},{"key":"ref86","doi-asserted-by":"publisher","first-page":"1283","DOI":"10.3390\/pharmaceutics14061283","article-title":"A historical review of brain drug delivery","volume":"14","author":"Pardridge","year":"2022","journal-title":"Pharmaceutics"},{"key":"ref87","doi-asserted-by":"publisher","first-page":"1366","DOI":"10.2174\/1381612824666171201115126","article-title":"Peptide mediated brain delivery of nano- and submicroparticles: a synergistic approach","volume":"24","author":"McCully","year":"2018","journal-title":"Curr Pharm Des"},{"key":"ref88","doi-asserted-by":"publisher","first-page":"4943","DOI":"10.1016\/j.biomaterials.2011.03.031","article-title":"Targeting the brain with PEG-PLGA nanoparticles modified with phage-displayed peptides","volume":"32","author":"Li","year":"2011","journal-title":"Biomaterials"},{"key":"ref89","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/s12987-025-00641-0","article-title":"PepH3-modified nanocarriers for delivery of therapeutics across the blood-brain barrier","volume":"22","author":"Szecsko","year":"2025","journal-title":"Fluids Barriers CNS"},{"key":"ref90","doi-asserted-by":"publisher","first-page":"5119","DOI":"10.1038\/s41598-022-09164-2","article-title":"Biomolecular engineering of drugs loading in riboflavin-targeted polymeric devices: simulation and experimental","volume":"12","author":"Khedri","year":"2022","journal-title":"Sci Rep"},{"key":"ref91","doi-asserted-by":"publisher","first-page":"950","DOI":"10.3390\/ijms21030950","article-title":"Riboflavin: the health benefits of a forgotten natural vitamin","volume":"21","author":"Suwannasom","year":"2020","journal-title":"Int J Mol Sci"},{"key":"ref92","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.nutres.2023.08.010","article-title":"Medicinal benefits, biological, and nanoencapsulation functions of riboflavin with its toxicity profile: a narrative review","volume":"119","author":"Lee","year":"2023","journal-title":"Nutr Res"},{"key":"ref93","doi-asserted-by":"publisher","first-page":"114820","DOI":"10.1016\/j.addr.2023.114820","article-title":"Engineered nanomaterials that exploit blood-brain barrier dysfunction for delivery to the brain","volume":"197","author":"Wu","year":"2023","journal-title":"Adv Drug Deliv Rev"},{"key":"ref94","doi-asserted-by":"publisher","first-page":"992986","DOI":"10.3389\/fnut.2022.992986","article-title":"Personalized nutrition: a review of genotype-based nutritional supplementation","volume":"9","author":"Wang","year":"2022","journal-title":"Front Nutr"},{"key":"ref95","doi-asserted-by":"publisher","first-page":"121","DOI":"10.3390\/jpm14121121","article-title":"The future of pharmacogenomics: integrating epigenetics, nutrigenomics, and beyond","volume":"14","author":"Shaman","year":"2024","journal-title":"J Pers Med"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2025.1663136\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T04:11:00Z","timestamp":1756786260000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2025.1663136\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,2]]},"references-count":95,"alternative-id":["10.3389\/fneur.2025.1663136"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2025.1663136","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,2]]},"article-number":"1663136"}}