Figure 4.

Multiple beneficial effects afforded by ROCK inhibition in prion diseases. In prion diseases, the pharmacological inhibition of ROCKs with Y-27632 or dimethylfasudil counteracts PrP^Sc neurotoxicity by rescuing (i) the neuronal polarity and connectivity through the restoration of cofilin-mediated actin severing, (ii) eIF2α-dependent protein translation through attenuation of PERK signaling, and (iii) the neuroprotective TACE α-secretase activity toward three main substrates: TNFR1, which restores physiological sensitivity to TNFα, PrP^C, and APP, which limits the accumulation of neurotoxic amyloids, i.e., PrP^Sc and Aβ.