Prion Efficiently Replicates in α-Synuclein Knockout Mice

  • Edoardo Bistaffa
  • Martina Rossi
  • Chiara Maria Giulia De Luca
  • Federico Cazzaniga
  • Olga Carletta
  • Ilaria Campagnani
  • Fabrizio Tagliavini
  • Giuseppe Legname
  • Giorgio Giaccone
  • Fabio ModaEmail author


Prion diseases are a group of neurodegenerative disorders associated with the conformational conversion of the cellular prion protein (PrPC) into an abnormal misfolded form named PrPSc. Other than accumulating in the brain, PrPSc can bind PrPC and force it to change conformation to PrPSc. The exact mechanism which underlies the process of PrPC/PrPSc conversion still needs to be defined and many molecules or cofactors might be involved. Several studies have documented an important role of PrPC to act as receptor for abnormally folded forms of α-synuclein which are responsible of a group of diseases known as synucleinopathies. The presence of PrPC was required to promote efficient internalization and spreading of abnormal α-synuclein between cells. In this work, we have assessed whether α-synuclein exerts any role in PrPSc conversion and propagation either in vitro or in vivo. Indeed, understanding the mechanism of PrPC/PrPSc conversion and the identification of cofactors involved in this process is crucial for developing new therapeutic strategies. Our results showed that PrPSc was able to efficiently propagate in the brain of animals even in the absence of α-synuclein thus suggesting that this protein did not act as key modulator of prion propagation. Thus, α-synuclein might take part in this process but is not specifically required for sustaining prion conversion and propagation.


Prions RML α-Synuclein PMCA 



The authors wish to thank Associazione Italiana Encefalopatie da Prioni (AIEnP).

Author Contributions

E.B. performed most of the experiments; M.R., C.D.L., performed part of the biochemical analysis; F.C., O.C. performed part of the histological analysis; I.C. was in charge of the animal care and sacrifice; F.T. and G.L. contributed in planning the experiments and in analyzing the data; and G.G. and F.M. supervised the work, analyzed the data and prepared the final version of the manuscript. All the authors read and approved the final manuscript.


This work was supported by the Italian Ministry of Health (RC) to F.M., Italian Ministry of Health to F.T., and Associazione Italiana Encefalopatie da Prioni (AIEnP).

Compliance with Ethical Standards

The study, including its Ethics aspects, was approved by the Italian Ministry of Health (Permit Number, NP-02-13).

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12035_2019_1602_MOESM1_ESM.jpg (632 kb)
ESM 1 (JPG 631 kb)


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Edoardo Bistaffa
    • 1
  • Martina Rossi
    • 2
  • Chiara Maria Giulia De Luca
    • 1
    • 2
  • Federico Cazzaniga
    • 1
  • Olga Carletta
    • 1
  • Ilaria Campagnani
    • 1
  • Fabrizio Tagliavini
    • 1
  • Giuseppe Legname
    • 2
  • Giorgio Giaccone
    • 1
  • Fabio Moda
    • 1
    Email author
  1. 1.Unit of Neuropathology and Neurology 5Fondazione IRCCS Istituto Neurologico Carlo BestaMilanItaly
  2. 2.Department of Neuroscience, Laboratory of Prion BiologyScuola Internazionale Superiore di Studi Avanzati (SISSA)TriesteItaly

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