Differential overexpression of SERPINA3 in human prion diseases

Silvia Vanni, F. Moda, Marco Zattoni, E Bistaffa, E De Cecco, M Rossi, G. Giaccone, F. Tagliavini, Stéphane Haïk, Jean-Philippe Deslys, Gianluigi Zanusso, J W Ironside, Isidre Ferrer, Gabor G. Kovacs, Giuseppe Legname

Research output: Contribution to journalArticlepeer-review

Abstract

Prion diseases are fatal neurodegenerative disorders with sporadic, genetic or acquired etiologies. The molecular alterations leading to the onset and the spreading of these diseases are still unknown. In a previous work we identified a five-gene signature able to distinguish intracranially BSE-infected macaques from healthy ones, with SERPINA3 showing the most prominent dysregulation. We analyzed 128 suitable frontal cortex samples, from prion-affected patients (variant Creutzfeldt-Jakob disease (vCJD) n = 20, iatrogenic CJD (iCJD) n = 11, sporadic CJD (sCJD) n = 23, familial CJD (gCJD) n = 17, fatal familial insomnia (FFI) n = 9, Gerstmann-Sträussler-Scheinker syndrome (GSS)) n = 4), patients with Alzheimer disease (AD, n = 14) and age-matched controls (n = 30). Real Time-quantitative PCR was performed for SERPINA3 transcript, and ACTB, RPL19, GAPDH and B2M were used as reference genes. We report SERPINA3 to be strongly up-regulated in the brain of all human prion diseases, with only a mild up-regulation in AD. We show that this striking up-regulation, both at the mRNA and at the protein level, is present in all types of human prion diseases analyzed, although to a different extent for each specific disorder. Our data suggest that SERPINA3 may be involved in the pathogenesis and the progression of prion diseases, representing a valid tool for distinguishing different forms of these disorders in humans.

Original languageEnglish
Pages (from-to)15637
JournalScientific Reports
Volume7
Issue number1
Early online date15 Nov 2017
DOIs
Publication statusE-pub ahead of print - 15 Nov 2017

Keywords

  • Journal Article

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