Differential overexpression of SERPINA3 in human prion diseases.

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.

SUBMITTER: Vanni S 

PROVIDER: S-EPMC5688139 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature