Prion Efficiently Replicates in α-Synuclein Knockout Mice

Prion diseases are a group of neurodegenerative disorders associated with the conformational conversion of the cellular prion protein (PrP^C) into an abnormal misfolded form named PrP^Sc. Other than accumulating in the brain, PrP^Sc can bind PrP^C and force it to change conformation to PrP^Sc. The exact mechanism which underlies the process of PrP^C/PrP^Sc conversion still needs to be defined and many molecules or cofactors might be involved. Several studies have documented an important role of PrP^C 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 PrP^C 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 PrP^Sc conversion and propagation either in vitro or in vivo. Indeed, understanding the mechanism of PrP^C/PrP^Sc conversion and the identification of cofactors involved in this process is crucial for developing new therapeutic strategies. Our results showed that PrP^Sc 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.