Prion diseases are
a group of neurodegenerative disorders characterized
by the accumulation of misfolded prion protein (called PrP
Sc
). Although conversion of the cellular prion protein (PrP
C
) to PrP
Sc
is still not completely understood, most of
the therapies developed until now are based on blocking this process.
Here, we propose a new drug strategy aimed at clearing prions without
any direct interaction with neither PrP
C
nor PrP
Sc
. Starting from the recent discovery of SERPINA3/SerpinA3n upregulation
during prion diseases, we have identified a small molecule, named
compound 5 (ARN1468), inhibiting the function of these serpins and
effectively reducing prion load in chronically infected cells. Although
the low bioavailability of this compound does not allow
in
vivo
studies in prion-infected mice, our strategy emerges
as a novel and effective approach to the treatment of prion disease.
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