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Sci Rep. 2017 Nov 15;7(1):15637. doi: 10.1038/s41598-017-15778-8.

Differential overexpression of SERPINA3 in human prion diseases.

Author information

1
Laboratory of Prion Biology, Department of Neuroscience, SISSA, Trieste, Italy.
2
Neurology and Neuropathology Unit, IRCCS Foundation Carlo Besta Neurological Institute, Milan, Italy.
3
Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, and CNRS UMR 7225, and ICM, Paris, France.
4
Atomic Energy Commission (CEA), DRF, Jacob, SEPIA, Fontenay-aux-Roses, France.
5
Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
6
National CJD Research & Surveillance Unit, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
7
Institute of Neuropathology, Bellvitge University Hospital, IDIBELL; Department of Pathology and Experimental Therapeutics, University of Barcelona; CIBERNED; Hospitalet de Llobregat, Llobregat, Spain.
8
Institute of Neurology, Medical University of Vienna, Vienna, Austria.
9
Laboratory of Prion Biology, Department of Neuroscience, SISSA, Trieste, Italy. legname@sissa.it.

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.

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