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Cobalamin (Cbl), also known as vitamin B<jats:sub>12<\/jats:sub>, is an essential micronutrient which mammals must acquire through diet, and neurologic dysfunction is a primary clinical manifestation of Cbl deficiency. Here we show that NRG\u20101 stimulates synthesis of the two bioactive Cbl species adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl) in human neuroblastoma cells by both promoting conversion of inactive to active Cbl species and increasing neuronal Cbl uptake. Formation of active Cbls is glutathione\u2010 (GSH\u2010) dependent and the NRG\u20101\u2010initiated increase is dependent upon its stimulation of cysteine uptake by excitatory amino acid transporter 3 (EAAT3), leading to increased GSH. The stimulatory effect of NRG\u20101 on cellular Cbl uptake is associated with increased expression of megalin, which is known to facilitate Cbl transport in ileum and kidney. MeCbl is a required cofactor for methionine synthase (MS) and we demonstrate the ability of NRG\u20101 to increase MS activity,  and affect levels of methionine methylation cycle metabolites. Our results identify novel neuroprotective roles of NRG\u20101 including stimulating antioxidant synthesis and promoting active Cbl formation.<\/jats:p>","DOI":"10.1155\/2016\/3849087","type":"journal-article","created":{"date-parts":[[2015,12,29]],"date-time":"2015-12-29T21:03:04Z","timestamp":1451422984000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Neuregulin 1 Promotes Glutathione\u2010Dependent Neuronal Cobalamin Metabolism by Stimulating Cysteine 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