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