Differential overexpression of SERPINA3 in human prion diseases

• Published in: Scientific reports 2017-11, Vol.7 (1), p.15637-13, Article 15637
• Main Authors: Vanni, S., Moda, F., Zattoni, M., Bistaffa, E., De Cecco, E., Rossi, M., Giaccone, G., Tagliavini, F., Haïk, S., Deslys, J. P., Zanusso, G., Ironside, J. W., Ferrer, I., Kovacs, G. G., Legname, G.
• Format: Article
• Language: English
• Subjects: 38; 38/39; 45; 45/77; 631/337/2019; 631/378/1689/364; 64; 64/60; 82; 82/51; 82/80; Adult; Aged; Alzheimer Disease - genetics; Alzheimer Disease - physiopathology; Alzheimer's disease; Animals; Bovine spongiform encephalopathy; Cortex (frontal); Creutzfeldt-Jakob disease; Creutzfeldt-Jakob Syndrome - genetics; Creutzfeldt-Jakob Syndrome - physiopathology; Female; Frontal Lobe - metabolism; Frontal Lobe - physiopathology; Gene Expression Regulation - genetics; Gerstmann-Straussler-Scheinker Disease - genetics; Gerstmann-Straussler-Scheinker Disease - physiopathology; Glyceraldehyde-3-phosphate dehydrogenase; Human health and pathology; Humanities and Social Sciences; Humans; Insomnia, Fatal Familial - genetics; Insomnia, Fatal Familial - physiopathology; Life Sciences; Male; Middle Aged; multidisciplinary; Neurodegenerative diseases; Prion Diseases - classification; Prion Diseases - genetics; Prion Diseases - physiopathology; Prions - genetics; Ribosomal Proteins - genetics; Science; Science (multidisciplinary); Serpins - genetics; Sleep disorders; Transcription
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-15778-8

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.