title: The epsilon isoform of 14-3-3 protein is a component of the prion protein amyloid deposits of Gerstmann-Sträussler-Scheinker disease.
abstract: The 14-3-3 proteins are highly conserved, ubiquitous molecules involved in a variety of biologic events, such as transduction pathway modulation, cell cycle control, and apoptosis. Seven isoforms have been identified that are abundant in the brain, preferentially localized in neurons. Remarkable increases in 14-3-3 are seen in the cerebrospinal fluid of patients with Creutzfeldt-Jakob disease (CJD), and it has been found in pathologic inclusions of several neurodegenerative diseases. Moreover, the zeta isoform has been detected in prion protein (PrP) amyloid deposits of CJD patients. To further investigate the cerebral distribution of 14-3-3 in prion-related encephalopathies, we carried out an immunohistochemical and biochemical analysis of brain tissue from patients with Gerstmann-Sträussler-Scheinker disease (GSS) and sporadic, familial and acquired forms of CJD, using specific antibodies against the seven 14-3-3 isoforms. The study showed a strong immunoreactivity of PrP amyloid plaques of GSS patients for the 14-3-3 epsilon isoform, but not for the other isoforms. The epsilon isoform of 14-3-3 was not found in PrP deposits of CJD. These results indicate that the epsilon isoform of 14-3-3 is a component of PrP amyloid deposits of GSS and suggest that this is the sole 14-3-3 isoform specifically involved in the neuropathologic changes associated with this disorder.
authors.affiliation: Department of Neuropathology and Neurology, Istituto Nazionale Neurologico Carlo Besta, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Fede
authors.forename: Giorgio
authors.initials: G
authors.lastname: Giaccone
authors.forename: Lucia
authors.initials: L
authors.lastname: Limido
authors.forename: Michela
authors.initials: M
authors.lastname: Mangieri
authors.forename: Silvia
authors.initials: S
authors.lastname: Suardi
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Puoti
authors.forename: Michela
authors.initials: M
authors.lastname: Morbin
authors.forename: Giulia
authors.initials: G
authors.lastname: Mazzoleni
authors.forename: Bernardino
authors.initials: B
authors.lastname: Ghetti
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Tagliavini
mesh_terms: D048948:14-3-3 Proteins / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D000918:Antibody Specificity; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007562:Creutzfeldt-Jakob Syndrome / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D003937:Diagnosis, Differential; D016098:Gerstmann-Straussler-Scheinker Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D058225:Plaque, Amyloid / Q000378:metabolism* / Q000473:pathology; D011237:Predictive Value of Tests; D011328:Prions / Q000378:metabolism*
chemical_list: D048948:14-3-3 Proteins; D015415:Biomarkers; D011328:Prions