[1]. According to the
“protein-only” hypothesis, the partly protease-resistant,
misfolded PrP, designated PrPSc, is the disease agent [2].
Prion diseases are entirely dependent on endogenous
PrP expression. For instance, PrP gene knockout mice
are resistant to prion disease [3], and further studies of
transgenic mice have shown that the level of PrP expression
is inversely correlated with the incubation time
[4,5]. In addition, knockdown of the PrP expression by
RNAi rescues early neuronal dysfunction and prolongs
survival time in mice with prion disease [6].