title: Relationships between cobalamin, epidermal growth factor, and normal prions in the myelin maintenance of central nervous system.
abstract: Cobalamin (Cbl), epidermal growth factor (EGF), and prions (PrPs) are key molecules for myelin maintenance in the central and peripheral nervous systems. Cbl and EGF increase normal prion (PrP(C)) synthesis and PrP(C) levels in rat spinal cord (SC) and elsewhere. Cbl deficiency increases PrP(C) levels in rat SC and cerebrospinal fluid (CSF), and decreases PrP(C)-mRNA levels in rat SC. The administration of anti-octapeptide repeat PrP(C) region antibodies (Abs) to Cbl-deficient (Cbl-D) rats prevents SC myelin lesions and a local increase in tumor necrosis factor (TNF)-α levels, whereas anti-TNF-α Abs prevent SC myelin lesions and the increase in SC and CSF PrP(C) levels. As it is known that both Cbl and EGF regulate SC PrP(C) synthesis independently, and that Cbl regulates SC EGF synthesis, EGF may play both Cbl-independent and Cbl-dependent roles. When Cbl-D rats undergo Cbl replacement therapy, SC PrP(C) levels are similar to those observed in Cbl-D rats. In rat frontal cortex (which is marginally affected by Cbl deficiency in histological terms), Cbl deficiency decreases PrP(C) levels and the increase induced by Cbl replacement leads to their normalization. Increased nerve PrP(C) levels are detected in the myelin lesions of the peripheral neuropathy of Cbl-D rats, and CSF PrP(C) levels are also increased in Cbl-D patients (but not in patients with Cbl-unrelated neurological diseases). Various common steps in the downstream signaling pathway of Cbl, EGF, and PrP(C) underlines the close relationship between the three molecules in keeping myelin normal.
authors.affiliation: Department of Biomedical Sciences, Laboratory of Neuropathology, University of Milan, 20133 Milano, Italy. Electronic address: giuseppe.scalabrino@unimi.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Scalabrino
authors.affiliation: Department of Biomedical Sciences, Laboratory of Neuropathology, University of Milan, 20133 Milano, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Veber
authors.affiliation: Department of Translational Medicine and Surgery, University of Milano-Bicocca, 20052 Monza, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tredici
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000378:metabolism*; D006801:Humans; D008959:Models, Neurological; D009186:Myelin Sheath / Q000378:metabolism*; D011328:Prions / Q000378:metabolism*; D015398:Signal Transduction; D016211:Transforming Growth Factor alpha / Q000378:metabolism; D014805:Vitamin B 12 / Q000378:metabolism*
chemical_list: D011328:Prions; D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor; D014805:Vitamin B 12
keywords: Cobalamin; Epidermal growth factor; Myelin; Normal prions; Tumor necrosis factor-α