{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T01:28:55Z","timestamp":1790386135667,"version":"4.1.0"},"reference-count":146,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,1,2]],"date-time":"2024-01-02T00:00:00Z","timestamp":1704153600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sapienza University of Rome","award":["RP12117A5C8B6DC1"],"award-info":[{"award-number":["RP12117A5C8B6DC1"]}]},{"name":"Sapienza University of Rome","award":["RP1221816749A2A8"],"award-info":[{"award-number":["RP1221816749A2A8"]}]},{"name":"Sapienza University of Rome","award":["RM12117A86B6FF27"],"award-info":[{"award-number":["RM12117A86B6FF27"]}]},{"name":"Sapienza University of Rome","award":["RM12117A895AFDD1"],"award-info":[{"award-number":["RM12117A895AFDD1"]}]},{"name":"Sapienza University of Rome","award":["AR123188A13167D9"],"award-info":[{"award-number":["AR123188A13167D9"]}]},{"name":"Sapienza University of Rome","award":["ARTICOLO 1, COMMI 314\u2013337 LEGGE 232\/2016"],"award-info":[{"award-number":["ARTICOLO 1, COMMI 314\u2013337 LEGGE 232\/2016"]}]},{"name":"Department of Science of Roma Tre University","award":["RP12117A5C8B6DC1"],"award-info":[{"award-number":["RP12117A5C8B6DC1"]}]},{"name":"Department of Science of Roma Tre University","award":["RP1221816749A2A8"],"award-info":[{"award-number":["RP1221816749A2A8"]}]},{"name":"Department of Science of Roma Tre University","award":["RM12117A86B6FF27"],"award-info":[{"award-number":["RM12117A86B6FF27"]}]},{"name":"Department of Science of Roma Tre University","award":["RM12117A895AFDD1"],"award-info":[{"award-number":["RM12117A895AFDD1"]}]},{"name":"Department of Science of Roma Tre University","award":["AR123188A13167D9"],"award-info":[{"award-number":["AR123188A13167D9"]}]},{"name":"Department of Science of Roma Tre University","award":["ARTICOLO 1, COMMI 314\u2013337 LEGGE 232\/2016"],"award-info":[{"award-number":["ARTICOLO 1, COMMI 314\u2013337 LEGGE 232\/2016"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Vitamin B12 (VitB12) is a micronutrient and acts as a cofactor for fundamental biochemical reactions: the synthesis of succinyl-CoA from methylmalonyl-CoA and biotin, and the synthesis of methionine from folic acid and homocysteine. VitB12 deficiency can determine a wide range of diseases, including nervous system impairments. Although clinical evidence shows a direct role of VitB12 in neuronal homeostasis, the molecular mechanisms are yet to be characterized in depth. Earlier investigations focused on exploring the biochemical shifts resulting from a deficiency in the function of VitB12 as a coenzyme, while more recent studies propose a broader mechanism, encompassing changes at the molecular\/cellular levels. Here, we explore existing study models employed to investigate the role of VitB12 in the nervous system, including the challenges inherent in replicating deficiency\/supplementation in experimental settings. Moreover, we discuss the potential biochemical alterations and ensuing mechanisms that might be modified at the molecular\/cellular level (such as epigenetic modifications or changes in lysosomal activity). We also address the role of VitB12 deficiency in initiating processes that contribute to nervous system deterioration, including ROS accumulation, inflammation, and demyelination. Consequently, a complex biological landscape emerges, requiring further investigative efforts to grasp the intricacies involved and identify potential therapeutic targets.<\/jats:p>","DOI":"10.3390\/ijms25010590","type":"journal-article","created":{"date-parts":[[2024,1,2]],"date-time":"2024-01-02T03:33:33Z","timestamp":1704166413000},"page":"590","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":94,"title":["Vitamin B12 Deficiency and the Nervous System: Beyond Metabolic Decompensation\u2014Comparing Biological Models and Gaining New Insights into Molecular and Cellular Mechanisms"],"prefix":"10.3390","volume":"25","author":[{"given":"Aimee Rachel","family":"Mathew","sequence":"first","affiliation":[{"name":"Department of Biology and Biotechnologies \u201cCharles Darwin\u201d, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0110-5010","authenticated-orcid":false,"given":"Giacomo","family":"Di Matteo","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Technology of Drugs, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9723-2363","authenticated-orcid":false,"given":"Piergiorgio","family":"La Rosa","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, Department of Psychology, Sapienza University of Rome, 00185 Rome, Italy"},{"name":"European Center for Brain Research, IRCCS Fondazione Santa Lucia, 00179 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saviana Antonella","family":"Barbati","sequence":"additional","affiliation":[{"name":"Departmental Faculty of Medicine and Surgery, UniCamillus-Saint Camillus International University of Health Sciences, 00131 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8659-5890","authenticated-orcid":false,"given":"Luisa","family":"Mannina","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Technology of Drugs, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1079-3222","authenticated-orcid":false,"given":"Sandra","family":"Moreno","sequence":"additional","affiliation":[{"name":"Department of Science, University Roma Tre, 00146 Rome, Italy"},{"name":"Laboratory of Neurodevelopment, Neurogenetics and Neuromolecular Biology, IRCCS Fondazione Santa Lucia, 00179 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4868-5435","authenticated-orcid":false,"given":"Ada Maria","family":"Tata","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnologies \u201cCharles Darwin\u201d, Sapienza University of Rome, 00185 Rome, Italy"},{"name":"Research Centre of Neurobiology \u201cDaniel Bovet\u201d, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virve","family":"Cavallucci","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina e Chirurgia Traslazionale, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1287-9601","authenticated-orcid":false,"given":"Marco","family":"Fidaleo","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnologies \u201cCharles Darwin\u201d, Sapienza University of Rome, 00185 Rome, Italy"},{"name":"Research Center for Nanotechnology Applied to Engineering (CNIS), Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.3181\/0703-MR-67","article-title":"Vitamin B12 Sources and Bioavailability","volume":"232","author":"Watanabe","year":"2007","journal-title":"Exp. Biol. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1159\/000343114","article-title":"The Discovery of Vitamin B12","volume":"61","author":"Scott","year":"2012","journal-title":"Ann. Nutr. Metab."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"54","DOI":"10.3945\/an.111.001370","article-title":"Vitamin B-12","volume":"3","author":"Allen","year":"2012","journal-title":"Adv. Nutr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1007\/978-94-007-2199-9_17","article-title":"Biochemistry of B12-Cofactors in Human Metabolism","volume":"Volume 56","year":"2012","journal-title":"Sub-Cellular Biochemistry"},{"key":"ref_5","first-page":"537","article-title":"B12 Deficiency: A Look beyond Pernicious Anemia","volume":"56","author":"Federici","year":"2007","journal-title":"J. Fam. Pract."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.amsu.2020.11.010","article-title":"Optic Neuropathy as a Presenting Feature of Vitamin B-12 Deficiency: A Systematic Review of Literature and a Case Report","volume":"60","author":"Ata","year":"2020","journal-title":"Ann. Med. Surg."},{"key":"ref_7","first-page":"e11169","article-title":"Vitamin B12 Supplementation: Preventing Onset and Improving Prognosis of Depression","volume":"12","author":"Sangle","year":"2020","journal-title":"Cureus"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1056\/NEJMcp1113996","article-title":"Vitamin B 12 Deficiency","volume":"368","author":"Stabler","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e92634","DOI":"10.5812\/ijp.92634","article-title":"Influence of Vitamin B12 Deficiency on Autonomic Nervous System Activity in Children","volume":"29","author":"Kayali","year":"2019","journal-title":"Iran. J. Pediatr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.neulet.2005.11.029","article-title":"Increased Spinal Cord NGF Levels in Rats with Cobalamin (Vitamin B12) Deficiency","volume":"396","author":"Scalabrino","year":"2006","journal-title":"Neurosci. Lett."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/sj.ejcn.1602490","article-title":"Nutritional Determinants of Plasma Total Homocysteine Distribution in the Canary Islands","volume":"61","author":"Doreste","year":"2007","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1002\/ajmg.c.30288","article-title":"Inborn Errors of Cobalamin Absorption and Metabolism","volume":"157","author":"Watkins","year":"2011","journal-title":"Am. J. Med. Genet. Part C Semin. Med. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.ymgmr.2016.01.005","article-title":"Successful Intrauterine Treatment of a Patient with Cobalamin C Defect","volume":"6","author":"Trefz","year":"2016","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1097\/PEC.0b013e318180ff32","article-title":"Neurological Consequences of Vitamin B12 Deficiency and Its Treatment","volume":"24","author":"Chalouhi","year":"2008","journal-title":"Pediatr. Emerg. Care"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1007\/s11596-020-2260-7","article-title":"Vitamin B(12) Deficiency in Newborns and Their Mothers-Novel Approaches to Early Detection, Treatment and Prevention of a Global Health Issue","volume":"40","author":"Gramer","year":"2020","journal-title":"Curr. Med. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.1021\/cr030720z","article-title":"Chemistry and Enzymology of Vitamin B 12","volume":"105","author":"Brown","year":"2005","journal-title":"Chem. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Osman, D., Cooke, A., Young, T.R., Deery, E., Robinson, N.J., and Warren, M.J. (2021). The Requirement for Cobalt in Vitamin B(12): A Paradigm for Protein Metalation. Biochim. Biophys. Acta Mol. Cell Res., 1868.","DOI":"10.1016\/j.bbamcr.2020.118896"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Hygum, K., Lildballe, D.L., Greibe, E.H., Morkbak, A.L., Poulsen, S.S., Sorensen, B.S., Petersen, T.E., and Nexo, E. (2011). Mouse Transcobalamin Has Features Resembling Both Human Transcobalamin and Haptocorrin. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0020638"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1182\/blood-2003-08-2852","article-title":"The Functional Cobalamin (Vitamin B12)\u2013Intrinsic Factor Receptor Is a Novel Complex of Cubilin and Amnionless","volume":"103","author":"Fyfe","year":"2004","journal-title":"Blood"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/nrgastro.2012.76","article-title":"Vitamin B 12 Transport from Food to the Body\u2019s Cells\u2014A Sophisticated, Multistep Pathway","volume":"9","author":"Nielsen","year":"2012","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1177\/26339447231152068","article-title":"Cerebral White Matter Demyelination in Vitamin B12 Deficiency: A Case Report","volume":"13","author":"Kumar","year":"2023","journal-title":"Indian J. Clin. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1038\/ng.2386","article-title":"Mutations in ABCD4 Cause a New Inborn Error of Vitamin B12 Metabolism","volume":"44","author":"Coelho","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Rizzo, G., and Lagan\u00e0, A.S. (2020). A Review of Vitamin B12. Mol. Nutr. Vitam., 105\u2013129.","DOI":"10.1016\/B978-0-12-811907-5.00005-1"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1111\/ejh.13571","article-title":"Review of Vitamin B12 Deficiency in Pregnancy: A Diagnosis Not to Miss as Veganism and Vegetarianism Become More Prevalent","volume":"106","author":"Rashid","year":"2021","journal-title":"Eur. J. Haematol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Lacombe, V., Lenaers, G., and Urbanski, G. (2022). Diagnostic and Therapeutic Perspectives Associated to Cobalamin-Dependent Metabolism and Transcobalamins\u2019 Synthesis in Solid Cancers. Nutrients, 14.","DOI":"10.3390\/nu14102058"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Boachie, J., Adaikalakoteswari, A., Goljan, I., Samavat, J., Cagampang, F.R., and Saravanan, P. (2021). Intracellular and Tissue Levels of Vitamin B12 in Hepatocytes Are Modulated by CD320 Receptor and TCN2 Transporter. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22063089"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"17040","DOI":"10.1038\/nrdp.2017.40","article-title":"Vitamin B(12) Deficiency","volume":"3","author":"Green","year":"2017","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_28","unstructured":"Ankar, A., and Kumar, A. (2022). Vitamin B12 Deficiency, StatPearls Publishing."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/j.cmet.2014.10.002","article-title":"Vitamin B12 as a Modulator of Gut Microbial Ecology","volume":"20","author":"Degnan","year":"2014","journal-title":"Cell Metab."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"7078","DOI":"10.3748\/wjg.v11.i45.7078","article-title":"Vitamin B12 deficiency and gastric histopathology in older patients","volume":"11","author":"Dholakia","year":"2005","journal-title":"World J. Gastroenterol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.abb.2007.03.011","article-title":"Cobalamin-Mediated Regulation of Transcobalamin Receptor Levels in Rat Organs","volume":"463","author":"Kalra","year":"2007","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Ge, Y., Zadeh, M., and Mohamadzadeh, M. (2022). Vitamin B12 Regulates the Transcriptional, Metabolic, and Epigenetic Programing in Human Ileal Epithelial Cells. Nutrients, 14.","DOI":"10.3390\/nu14142825"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e20220057","DOI":"10.1084\/jem.20220057","article-title":"Vitamin B12 Coordinates Ileal Epithelial Cell and Microbiota Functions to Resist Salmonella Infection in Mice","volume":"219","author":"Ge","year":"2022","journal-title":"J. Exp. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"83","DOI":"10.3389\/fnut.2020.00083","article-title":"Vitamin B12 Deficiency Alters the Gut Microbiota in a Murine Model of Colitis","volume":"7","author":"Lurz","year":"2020","journal-title":"Front. Nutr."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Boachie, J., Adaikalakoteswari, A., Samavat, J., and Saravanan, P. (2020). Low Vitamin B12 and Lipid Metabolism: Evidence from Pre-Clinical and Clinical Studies. Nutrients, 12.","DOI":"10.3390\/nu12071925"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1038\/ejcn.2013.232","article-title":"Vitamin B12: One Carbon Metabolism, Fetal Growth and Programming for Chronic Disease","volume":"68","author":"Rush","year":"2014","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ydbio.2020.09.005","article-title":"Mouse Models to Study the Pathophysiology of Combined Methylmalonic Acidemia and Homocystinuria, CblC Type","volume":"468","author":"Chern","year":"2020","journal-title":"Dev. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1203\/PDR.0b013e3181e5c3a4","article-title":"Succinyl-CoA Ligase Deficiency: A Mitochondrial Hepatoencephalomyopathy","volume":"68","author":"Saenz","year":"2010","journal-title":"Pediatr. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"E259","DOI":"10.1152\/ajpendo.2000.279.2.E259","article-title":"Malonyl-CoA Content and Fatty Acid Oxidation in Rat Muscle and Liver in Vivo","volume":"279","author":"Chien","year":"2000","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e37","DOI":"10.1017\/S1462399410001651","article-title":"Genetic Disorders of Vitamin B\u2081\u2082 Metabolism: Eight Complementation Groups\u2014Eight Genes","volume":"12","author":"Froese","year":"2010","journal-title":"Expert Rev. Mol. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1002\/glia.23271","article-title":"Bioenergetic Regulation of Microglia","volume":"66","author":"Ghosh","year":"2018","journal-title":"Glia"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.redox.2013.12.026","article-title":"A Review of the Mitochondrial and Glycolytic Metabolism in Human Platelets and Leukocytes: Implications for Their Use as Bioenergetic Biomarkers","volume":"2","author":"Kramer","year":"2014","journal-title":"Redox Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.ccr.2004.11.022","article-title":"Succinate Links TCA Cycle Dysfunction to Oncogenesis by Inhibiting HIF-Alpha Prolyl Hydroxylase","volume":"7","author":"Selak","year":"2005","journal-title":"Cancer Cell"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1038\/nature11986","article-title":"Succinate Is an Inflammatory Signal That Induces IL-1\u03b2 through HIF-1\u03b1","volume":"496","author":"Tannahill","year":"2013","journal-title":"Nature"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"29318","DOI":"10.1074\/jbc.M002725200","article-title":"Increase in Plasma Homocysteine Associated with Parallel Increases in Plasma S-Adenosylhomocysteine and Lymphocyte DNA Hypomethylation","volume":"275","author":"Yi","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"van de Lagemaat, E.E., de Groot, L.C.P.G.M., and van den Heuvel, E.G.H.M. (2019). Vitamin B(12) in Relation to Oxidative Stress: A Systematic Review. Nutrients, 11.","DOI":"10.3390\/nu11020482"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"6043038","DOI":"10.1155\/2016\/6043038","article-title":"Hydrogen Sulfide and Cellular Redox Homeostasis","volume":"2016","author":"Xie","year":"2016","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Lildballe, D.L., Mutti, E., Birn, H., and Nexo, E. (2012). Maximal Load of the Vitamin B12 Transport System: A Study on Mice Treated for Four Weeks with High-Dose Vitamin B12 or Cobinamide. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0046657"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Mutti, E., Ruetz, M., Birn, H., Kr\u00e4utler, B., and Nexo, E. (2013). 4-Ethylphenyl-Cobalamin Impairs Tissue Uptake of Vitamin B12 and Causes Vitamin B12 Deficiency in Mice. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0075312"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1038\/s41467-021-27759-7","article-title":"Mutations in Hcfc1 and Ronin Result in an Inborn Error of Cobalamin Metabolism and Ribosomopathy","volume":"13","author":"Chern","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1096\/fasebj.13.2.297","article-title":"Myelinolytic Lesions in Spinal Cord of Cobalamin-deficient Rats Are TNF-\u03b1-mediated","volume":"13","author":"Buccellato","year":"1999","journal-title":"FASEB J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1016\/S0140-6736(78)92314-0","article-title":"Animal Model For Subacute Combined Degeneration","volume":"312","author":"Dinn","year":"1978","journal-title":"Lancet"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.diff.2023.04.003","article-title":"Abnormal Chondrocyte Development in a Zebrafish Model of CblC Syndrome Restored by an MMACHC Cobalamin Binding Mutant","volume":"131","author":"Paz","year":"2023","journal-title":"Differentiation"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.1093\/hmg\/ddaa044","article-title":"The Vitamin B12 Processing Enzyme, Mmachc, Is Essential for Zebrafish Survival, Growth and Retinal Morphology","volume":"29","author":"Sloan","year":"2020","journal-title":"Hum. Mol. Genet."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Arigony, A.L.V., de Oliveira, I.M., Machado, M., Bordin, D.L., Bergter, L., Pr\u00e1, D., and Henriques, J.A.P. (2013). The Influence of Micronutrients in Cell Culture: A Reflection on Viability and Genomic Stability. Biomed. Res. Int., 2013.","DOI":"10.1155\/2013\/597282"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.clinbiochem.2003.08.004","article-title":"Significance of Elevated Cobalamin (Vitamin B12) Levels in Blood","volume":"36","author":"Ermens","year":"2003","journal-title":"Clin. Biochem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"348S","DOI":"10.3945\/ajcn.111.013441","article-title":"Biomarkers of Cobalamin (Vitamin B-12) Status in the Epidemiologic Setting: A Critical Overview of Context, Applications, and Performance Characteristics of Cobalamin, Methylmalonic Acid, and Holotranscobalamin II","volume":"94","author":"Carmel","year":"2011","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Fidaleo, M., Tacconi, S., Sbarigia, C., Passeri, D., Rossi, M., Tata, A.M., and Dini, L. (2021). Current Nanocarrier Strategies Improve Vitamin B12 Pharmacokinetics, Ameliorate Patients\u2019 Lives, and Reduce Costs. Nanomaterials, 11.","DOI":"10.3390\/nano11030743"},{"key":"ref_59","unstructured":"Kovalevich, J., and Langford, D. (2013). Neuronal Cell Culture: Methods and Protocols, Springer."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Dastidar, R., and Sikder, K. (2022). Diagnostic Reliability of Serum Active B12 (Holo-Transcobalamin) in True Evaluation of Vitamin B12 Deficiency: Relevance in Current Perspective. BMC Res. Notes, 15.","DOI":"10.1186\/s13104-022-06224-8"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1632","DOI":"10.1182\/blood-2009-07-232587","article-title":"Identification of Multidrug Resistance Protein 1 (MRP1\/ABCC1) as a Molecular Gate for Cellular Export of Cobalamin","volume":"115","author":"Hardlei","year":"2010","journal-title":"Blood"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1046\/j.1365-2249.1999.00870.x","article-title":"Immunomodulation by Vitamin B12: Augmentation of CD8+ T Lymphocytes and Natural Killer (NK) Cell Activity in Vitamin B12-Deficient Patients by Methyl-B12 Treatment","volume":"116","author":"Tamura","year":"1999","journal-title":"Clin. Exp. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Jonnalagadda, D., Kihara, Y., Groves, A., Ray, M., and Saha, A. (2022). FTY720 Requires Vitamin B 12 -TCN2-CD320 Signaling in Astrocytes to Reduce Disease in an Animal Model of Multiple Sclerosis. bioRxiv.","DOI":"10.1101\/2022.01.10.475450"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.jneumeth.2013.04.008","article-title":"Analysis of Subcellular [57Co] Cobalamin Distribution in SH-SY5Y Neurons and Brain Tissue","volume":"217","author":"Zhao","year":"2013","journal-title":"J. Neurosci. Methods"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.3233\/JAD-140681","article-title":"Impaired Lysosomal Cobalamin Transport in Alzheimer\u2019s Disease","volume":"43","author":"Zhao","year":"2015","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"17606","DOI":"10.1074\/jbc.RA118.005323","article-title":"Functional and phylogenetic characterization of noncanonical vitamin B12-binding proteins in zebrafish suggests involvement in cobalamin transport","volume":"293","author":"Benoit","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/ng1683","article-title":"Identification of the Gene Responsible for Methylmalonic Aciduria and Homocystinuria, CblC Type","volume":"38","author":"Tirone","year":"2006","journal-title":"Nat. Genet."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s10545-011-9364-y","article-title":"Combined Methylmalonic Acidemia and Homocystinuria, CblC Type. I. Clinical Presentations, Diagnosis and Management","volume":"35","author":"Chandler","year":"2012","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s10545-010-9161-z","article-title":"Cobalamin C Defect: Natural History, Pathophysiology, and Treatment","volume":"34","author":"Martinelli","year":"2011","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.ymgme.2015.01.012","article-title":"Ocular Disease in the Cobalamin C Defect: A Review of the Literature and a Suggested Framework for Clinical Surveillance","volume":"114","author":"McCourt","year":"2015","journal-title":"Mol. Genet. Metab."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.ymgme.2010.10.011","article-title":"Interaction between MMACHC and MMADHC, Two Human Proteins Participating in Intracellular Vitamin B\u2081\u2082 Metabolism","volume":"102","author":"Plesa","year":"2011","journal-title":"Mol. Genet. Metab."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"29167","DOI":"10.1074\/jbc.M115.683268","article-title":"Structural Insights into the MMACHC-MMADHC Protein Complex Involved in Vitamin B12 Trafficking","volume":"290","author":"Froese","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"896177","DOI":"10.3389\/fped.2022.896177","article-title":"Case Report: A Case of Late-Onset Combined Methylmalonic Acidemia and Hyperhomocysteinemia Induced by a Vegetarian Diet","volume":"10","author":"Xu","year":"2022","journal-title":"Front. Pediatr."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.jns.2012.04.012","article-title":"A Clinical and Gene Analysis of Late-Onset Combined Methylmalonic Aciduria and Homocystinuria, CblC Type, in China","volume":"318","author":"Wang","year":"2012","journal-title":"J. Neurol. Sci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2430","DOI":"10.1002\/ajmg.a.31932","article-title":"Late-Onset Combined Homocystinuria and Methylmalonic Aciduria (CblC) and Neuropsychiatric Disturbance","volume":"143A","author":"Tsai","year":"2007","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_76","first-page":"871","article-title":"Late-Onset Methylmalonic Acidemia and Homocysteinemia","volume":"38","author":"Arhip","year":"2021","journal-title":"Nutr. Hosp."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"492","DOI":"10.4103\/0366-6999.199826","article-title":"Manic-Depressive Psychosis as the Initial Symptom in Adult Siblings with Late-Onset Combined Methylmalonic Aciduria and Homocystinemia, Cobalamin C Type","volume":"130","author":"Wu","year":"2017","journal-title":"Chin. Med. J."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1186\/s13023-014-0161-1","article-title":"Three New Cases of Late-Onset CblC Defect and Review of the Literature Illustrating When to Consider Inborn Errors of Metabolism beyond Infancy","volume":"9","author":"Huemer","year":"2014","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/j.semcdb.2011.05.005","article-title":"B12 in Fetal Development","volume":"22","author":"Pepper","year":"2011","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Cruz-Rodr\u00edguez, J., D\u00edaz-L\u00f3pez, A., Canals-Sans, J., and Arija, V. (2023). Maternal Vitamin B12 Status during Pregnancy and Early Infant Neurodevelopment: The ECLIPSES Study. Nutrients, 15.","DOI":"10.3390\/nu15061529"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/cns.13207","article-title":"B Vitamins in the Nervous System: Current Knowledge of the Biochemical Modes of Action and Synergies of Thiamine, Pyridoxine, and Cobalamin","volume":"26","year":"2020","journal-title":"CNS Neurosci. Ther."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"110525","DOI":"10.1016\/j.intimp.2023.110525","article-title":"Vitamin B Complex Suppresses Neuroinflammation in Activated Microglia: In Vitro and in Silico Approach Combined with Dynamical Modeling","volume":"121","author":"Graovac","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/S0014-5793(01)03030-7","article-title":"Gene Silencing by S-Adenosylmethionine in Muscle Differentiation","volume":"508","author":"Fuso","year":"2001","journal-title":"FEBS Lett."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.mcn.2004.09.007","article-title":"S-Adenosylmethionine\/Homocysteine Cycle Alterations Modify DNA Methylation Status with Consequent Deregulation of PS1 and BACE and Beta-Amyloid Production","volume":"28","author":"Fuso","year":"2005","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/S0014-5793(03)00277-1","article-title":"Presenilin 1 Gene Silencing by S-Adenosylmethionine: A Treatment for Alzheimer Disease?","volume":"541","author":"Scarpa","year":"2003","journal-title":"FEBS Lett."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Ghosh, S., Ali, R., and Verma, S. (2023). A\u03b2-Oligomers: A Potential Therapeutic Target for Alzheimer\u2019s Disease. Int. J. Biol. Macromol., 239.","DOI":"10.1016\/j.ijbiomac.2023.124231"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"527","DOI":"10.2174\/156720512800618053","article-title":"PSEN1 Promoter Demethylation in Hyperhomocysteinemic TgCRND8 Mice Is the Culprit, Not the Consequence","volume":"9","author":"Fuso","year":"2012","journal-title":"Curr. Alzheimer Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.2353\/ajpath.2009.081036","article-title":"Hyperhomocysteinemia Increases Beta-Amyloid by Enhancing Expression of Gamma-Secretase and Phosphorylation of Amyloid Precursor Protein in Rat Brain","volume":"174","author":"Zhang","year":"2009","journal-title":"Am. J. Pathol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"101546","DOI":"10.1016\/j.disamonth.2023.101546","article-title":"Association of Alzheimer\u2019s Dementia with Oral Bacteria, Vitamin B12, Folate, Homocysteine Levels, and Insulin Resistance along with Its Pathophysiology, Genetics, Imaging, and Biomarkers","volume":"69","author":"Prajjwal","year":"2023","journal-title":"Dis. Mon."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.ijbiomac.2017.03.001","article-title":"Vitamin B12 Offers Neuronal Cell Protection by Inhibiting A\u03b2-42 Amyloid Fibrillation","volume":"99","author":"Alam","year":"2017","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1002\/cphc.202100124","article-title":"The Role of Amyloid \u03b2-Biomembrane Interactions in the Pathogenesis of Alzheimer\u2019s Disease: Insights from Liposomes as Membrane Models","volume":"22","author":"Andrade","year":"2021","journal-title":"Chemphyschem"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1034\/j.1600-0609.2001.t01-1-00507.x","article-title":"Human Cobalamin Deficiency: Alterations in Serum Tumour Necrosis Factor-Alpha and Epidermal Growth Factor","volume":"67","author":"Peracchi","year":"2001","journal-title":"Eur. J. Haematol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1002\/jnr.21599","article-title":"Indirect Down-Regulation of Nuclear NF-KappaB Levels by Cobalamin in the Spinal Cord and Liver of the Rat","volume":"86","author":"Veber","year":"2008","journal-title":"J. Neurosci. Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1515\/CCLM.2003.220","article-title":"New Basis of the Neurotrophic Action of Vitamin B12","volume":"41","author":"Scalabrino","year":"2003","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.brainres.2010.03.073","article-title":"Loss of Epidermal Growth Factor Regulation by Cobalamin in Multiple Sclerosis","volume":"1333","author":"Scalabrino","year":"2010","journal-title":"Brain Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.brainres.2010.12.056","article-title":"Cobalamin Deficiency-Induced Changes of Epidermal Growth Factor (EGF)-Receptor Expression and EGF Levels in Rat Spinal Cord","volume":"1376","author":"Mutti","year":"2011","journal-title":"Brain Res."},{"key":"ref_97","first-page":"3136","article-title":"Combined Inadequacies of Multiple B Vitamins Amplify Colonic Wnt Signaling and Promote Intestinal Tumorigenesis in BAT-LacZxApc1638N Mice","volume":"25","author":"Liu","year":"2011","journal-title":"FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1111\/cns.13206","article-title":"Inhibition of Activator Protein 1 Attenuates Neuroinflammation and Brain Injury after Experimental Intracerebral Hemorrhage","volume":"25","author":"Wei","year":"2019","journal-title":"CNS Neurosci. Ther."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"21930","DOI":"10.1073\/pnas.0811794106","article-title":"Vitamin B12 Deficiency Reduces Proliferation and Promotes Differentiation of Neuroblastoma Cells and Up-Regulates PP2A, ProNGF, and TACE","volume":"106","author":"Akchiche","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/nrn3504","article-title":"NMDA Receptor Subunit Diversity: Impact on Receptor Properties, Synaptic Plasticity and Disease","volume":"14","author":"Paoletti","year":"2013","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.ejphar.2008.11.059","article-title":"Cyanocobalamin, Vitamin B12, Depresses Glutamate Release through Inhibition of Voltage-Dependent Ca2+ Influx in Rat Cerebrocortical Nerve Terminals (Synaptosomes)","volume":"602","author":"Hung","year":"2009","journal-title":"Eur. J. Pharmacol."},{"key":"ref_102","first-page":"61","article-title":"Modulation of hippocampal glutamate and NMDA\/AMPA receptor by homocysteine in chronic unpredictable mild stress-induced rat depression","volume":"65","author":"Liu","year":"2013","journal-title":"Sheng Li Xue Bao"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.neuropharm.2007.05.018","article-title":"Regulation of NMDA Receptors by Phosphorylation","volume":"53","author":"Chen","year":"2007","journal-title":"Neuropharmacology"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Roth, W., and Mohamadzadeh, M. (2021). Vitamin B12 and Gut-Brain Homeostasis in the Pathophysiology of Ischemic Stroke. EBioMedicine, 73.","DOI":"10.1016\/j.ebiom.2021.103676"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1089\/ars.2010.3474","article-title":"Significance of Brain Tissue Oxygenation and the Arachidonic Acid Cascade in Stroke","volume":"14","author":"Rink","year":"2011","journal-title":"Antioxid. Redox Signal."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1179\/1476830515Y.0000000041","article-title":"Novel Relationships between B12, Folate and Markers of Inflammation, Oxidative Stress and NAD(H) Levels, Systemically and in the CNS of a Healthy Human Cohort","volume":"18","author":"Guest","year":"2015","journal-title":"Nutr. Neurosci."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"152953","DOI":"10.1016\/j.prp.2020.152953","article-title":"Synaptic Remodeling and Reduced Expression of the Transcription Factors, HES1 and HES5, in the Cortex Neurons of Cognitively Impaired Hyperhomocysteinemic Mice","volume":"216","author":"Zhang","year":"2020","journal-title":"Pathol. Res. Pract."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"105109","DOI":"10.1016\/j.jstrokecerebrovasdis.2020.105109","article-title":"High-Concentration Homocysteine Inhibits Mitochondrial Respiration Function and Production of Reactive Oxygen Species in Neuron Cells","volume":"29","author":"Zhang","year":"2020","journal-title":"J. Stroke Cerebrovasc. Dis. Off. J. Natl. Stroke Assoc."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"146592","DOI":"10.1016\/j.brainres.2019.146592","article-title":"Chronic Mild Hyperhomocysteinemia Induces Anxiety-like Symptoms, Aversive Memory Deficits and Hippocampus Atrophy in Adult Rats: New Insights into Physiopathological Mechanisms","volume":"1728","author":"Wyse","year":"2020","journal-title":"Brain Res."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1007\/s12272-018-1016-4","article-title":"Causes of Hyperhomocysteinemia and Its Pathological Significance","volume":"41","author":"Kim","year":"2018","journal-title":"Arch. Pharm. Res."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Molognoni, F., de Melo, F.H.M., da Silva, C.T., and Jasiulionis, M.G. (2013). Ras and Rac1, Frequently Mutated in Melanomas, Are Activated by Superoxide Anion, Modulate Dnmt1 Level and Are Causally Related to Melanocyte Malignant Transformation. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0081937"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/s12974-020-01763-y","article-title":"Vitamin B(12) Is Neuroprotective in Experimental Pneumococcal Meningitis through Modulation of Hippocampal DNA Methylation","volume":"17","author":"Lopes","year":"2020","journal-title":"J. Neuroinflammation"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s10142-023-00969-6","article-title":"Altered Vitamin B12 Metabolism in the Central Nervous System Is Associated with the Modification of Ribosomal Gene Expression: New Insights from Comparative RNA Dataset Analysis","volume":"23","author":"Mathew","year":"2023","journal-title":"Funct. Integr. Genom."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"22635","DOI":"10.1038\/srep22635","article-title":"Quantitative Proteomics Study of the Neuroprotective Effects of B12 on Hydrogen Peroxide-Induced Apoptosis in SH-SY5Y Cells","volume":"6","author":"Zhong","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.freeradbiomed.2009.04.023","article-title":"A Novel Role for Vitamin B(12): Cobalamins Are Intracellular Antioxidants in Vitro","volume":"47","author":"Birch","year":"2009","journal-title":"Free Radic. Biol. Med."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.redox.2018.08.003","article-title":"Hippocampal Neurons Require a Large Pool of Glutathione to Sustain Dendrite Integrity and Cognitive Function","volume":"19","author":"Resch","year":"2018","journal-title":"Redox Biol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"109356","DOI":"10.1016\/j.mehy.2019.109356","article-title":"A Diet Rich in Taurine, Cysteine, Folate, B(12) and Betaine May Lessen Risk for Alzheimer\u2019s Disease by Boosting Brain Synthesis of Hydrogen Sulfide","volume":"132","author":"McCarty","year":"2019","journal-title":"Med. Hypotheses"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"360438","DOI":"10.1155\/2014\/360438","article-title":"Lipid Peroxidation: Production, Metabolism, and Signaling Mechanisms of Malondialdehyde and 4-Hydroxy-2-Nonenal","volume":"2014","author":"Ayala","year":"2014","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"7713","DOI":"10.1016\/j.chroma.2011.07.073","article-title":"From Brain to Food: Analysis of Phosphatidylcholins, Lyso-Phosphatidylcholins and Phosphatidylcholin-Plasmalogens Derivates in Alzheimer\u2019s Disease Human Post Mortem Brains and Mice Model via Mass Spectrometry","volume":"1218","author":"Grimm","year":"2011","journal-title":"J. Chromatogr. A"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1016\/j.bbamem.2018.03.015","article-title":"Role of the Cell Membrane Interface in Modulating Production and Uptake of Alzheimer\u2019s Beta Amyloid Protein","volume":"1860","author":"Bharadwaj","year":"2018","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.jalz.2013.05.1771","article-title":"Plasma Nutrient Status of Patients with Alzheimer\u2019s Disease: Systematic Review and Meta-Analysis","volume":"10","author":"Vellas","year":"2014","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"777","DOI":"10.3233\/JAD-150140","article-title":"Associations between Homocysteine, Folic Acid, Vitamin B12 and Alzheimer\u2019s Disease: Insights from Meta-Analyses","volume":"46","author":"Shen","year":"2015","journal-title":"J. Alzheimer\u2019s. Dis."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1016\/S0197-4580(03)00005-8","article-title":"Combination of Serum Markers Related to Several Mechanisms in Alzheimer\u2019s Disease","volume":"24","author":"Teunissen","year":"2003","journal-title":"Neurobiol. Aging"},{"key":"ref_124","first-page":"249","article-title":"Effects of Folic Acid and Vitamin B12 Supplementation on Cognitive Impairment and Inflammation in Patients with Alzheimer\u2019s Disease: A Randomized, Single-Blinded, Placebo-Controlled Trial","volume":"8","author":"Chen","year":"2021","journal-title":"J. Prev. Alzheimer\u2019s Dis."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"395","DOI":"10.3233\/JAD-142499","article-title":"A Phase II Randomized Clinical Trial of a Nutritional Formulation for Cognition and Mood in Alzheimer\u2019s Disease","volume":"45","author":"Remington","year":"2015","journal-title":"J. Alzheimer\u2019s. Dis."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Theiss, E.L., Griebsch, L.V., Lauer, A.A., Janitschke, D., Erhardt, V.K.J., Haas, E.C., Kuppler, K.N., Radermacher, J., Walzer, O., and Portius, D. (2022). Vitamin B12 Attenuates Changes in Phospholipid Levels Related to Oxidative Stress in SH-SY5Y Cells. Cells, 11.","DOI":"10.3390\/cells11162574"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"4837","DOI":"10.2147\/DDDT.S336066","article-title":"Methylcobalamin Protects Melanocytes from H2O2-Induced Oxidative Stress by Activating the Nrf2\/HO-1 Pathway","volume":"15","author":"An","year":"2021","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_128","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_129","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/s41573-018-0008-x","article-title":"Therapeutic Targeting of the NRF2 and KEAP1 Partnership in Chronic Diseases","volume":"18","author":"Cuadrado","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"La Rosa, P., Petrillo, S., Bertini, E.S., and Piemonte, F. (2020). Oxidative Stress in DNA Repeat Expansion Disorders: A Focus on NRF2 Signaling Involvement. Biomolecules, 10.","DOI":"10.3390\/biom10050702"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"e2513","DOI":"10.1038\/cddis.2016.374","article-title":"Hyperhomocysteinemia Causes ER Stress and Impaired Autophagy That Is Reversed by Vitamin B Supplementation","volume":"7","author":"Tripathi","year":"2016","journal-title":"Cell Death Dis."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1080\/00207454.2021.1962863","article-title":"The Effect of Vitamin B12 on Synaptic Plasticity of Hippocampus in Alzheimer\u2019s Disease Model Rats","volume":"133","author":"Mehrdad","year":"2023","journal-title":"Int. J. Neurosci."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1038\/s41594-020-00537-7","article-title":"TDP-43 Aggregation Induced by Oxidative Stress Causes Global Mitochondrial Imbalance in ALS","volume":"28","author":"Zuo","year":"2021","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Jeon, Y.-M., Kwon, Y., Lee, S., Kim, S., Jo, M., Lee, S., Kim, S.R., Kim, K., and Kim, H.-J. (2021). Vitamin B12 Reduces TDP-43 Toxicity by Alleviating Oxidative Stress and Mitochondrial Dysfunction. Antioxidants, 11.","DOI":"10.3390\/antiox11010082"},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Jeong, G.R., and Lee, B.D. (2020). Pathological Functions of LRRK2 in Parkinson\u2019s Disease. Cells, 9.","DOI":"10.3390\/cells9122565"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/s41422-019-0153-8","article-title":"Vitamin B(12) Modulates Parkinson\u2019s Disease LRRK2 Kinase Activity through Allosteric Regulation and Confers Neuroprotection","volume":"29","author":"Schaffner","year":"2019","journal-title":"Cell Res."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"2105152","DOI":"10.1002\/adfm.202105152","article-title":"Treating LRRK2-Related Parkinson\u2019s Disease by Inhibiting the MTOR Signaling Pathway to Restore Autophagy","volume":"31","author":"Cui","year":"2021","journal-title":"Adv. Funct. Mater."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"2563","DOI":"10.1096\/fj.201800754RR","article-title":"V Neuropathology of Vitamin B 12 Deficiency in the Cd320\u2212\/\u2212 Mouse","volume":"33","author":"Arora","year":"2019","journal-title":"FASEB J."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"37","DOI":"10.7326\/0003-4819-142-1-200501040-00110","article-title":"Meta-Analysis: High-Dosage Vitamin E Supplementation May Increase All-Cause Mortality","volume":"142","author":"Miller","year":"2005","journal-title":"Ann. Intern. Med."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"ENEURO.0239-18.2018","DOI":"10.1523\/ENEURO.0239-18.2018","article-title":"A Functionally Defined In Vivo Astrocyte Population Identified by C-Fos Activation in a Mouse Model of Multiple Sclerosis Modulated by S1P Signaling: Immediate-Early Astrocytes (IeAstrocytes)","volume":"5","author":"Groves","year":"2018","journal-title":"eNeuro"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"4521","DOI":"10.3390\/nu5114521","article-title":"Cobalamin Deficiency: Clinical Picture and Radiological Findings","volume":"5","author":"Briani","year":"2013","journal-title":"Nutrients"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s41936-020-00148-0","article-title":"Deficiency of Vitamin B12 and Its Relation with Neurological Disorders: A Critical Review","volume":"81","author":"Nawaz","year":"2020","journal-title":"J. Basic Appl. Zool."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.brainresrev.2008.05.001","article-title":"Experimental and Clinical Evidence of the Role of Cytokines and Growth Factors in the Pathogenesis of Acquired Cobalamin-Deficient Leukoneuropathy","volume":"59","author":"Scalabrino","year":"2008","journal-title":"Brain Res. Rev."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"E11807","DOI":"10.1073\/pnas.1808064115","article-title":"The Adult Oligodendrocyte Can Participate in Remyelination","volume":"115","author":"Duncan","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"298","DOI":"10.3389\/fncel.2015.00298","article-title":"Methylcobalamin Promotes the Differentiation of Schwann Cells and Remyelination in Lysophosphatidylcholine-Induced Demyelination of the Rat Sciatic Nerve","volume":"9","author":"Nishimoto","year":"2015","journal-title":"Front. Cell. Neurosci."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"5031","DOI":"10.3390\/nu5125031","article-title":"Neuroenhancement with Vitamin B12-Underestimated Neurological Significance","volume":"5","author":"Kisters","year":"2013","journal-title":"Nutrients"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/1\/590\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:38:17Z","timestamp":1760103497000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/1\/590"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,2]]},"references-count":146,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["ijms25010590"],"URL":"https:\/\/doi.org\/10.3390\/ijms25010590","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,2]]}}}