Fig. 6: A model.
From: Cathepsin B promotes Aβ proteotoxicity by modulating aging regulating mechanisms
The activity of CPR-6 (Cathepsin B) is modulated by aging (i). CPR-6 protects worms from the toxicity of polyQ35 stretches (ii) but exacerbates Aβ proteotoxicity. Accordingly, the knockdown of cpr-6 mitigates the toxicity of Aβ. The counter-proteotoxic effect of cpr-6 RNAi is linked with increased levels of SMK-1 protein (iii), which probably cooperates with SKN-1 (iv), and with reduced expression of the swsn-3 gene (v) which encodes for a chromatin modulator. SWSN-3 is predicted to be important for the proteostasis-maintaining activity of SKN-1 (vi) by modulating gene expression (vii). This modulation mitigates Aβ proteotoxicity (viii), possibly by the modification of nuclear import and organization.
