Niclosamide blocks autophagy via lysosomal dysfunction (663.18)

Niclosamide is a salicylanilide derivative used as antihelminthic agent. Recently, Nic has been screened out as an autophagy modulator by us and other groups and was identified to be a structurally distinct mTORC1 signaling inhibitor. In this work, we measured the long-lived protein degradation activity and found Niclosamide could inhibit the autophagic process. To elucidate the inhibition of Niclosamide on autophagy, we further tested the lysosomal activity using DQ-BSA assay and measured protease activity such as Cathepsin B and Cathepsin D with fluorescent substrates. The lower degradation of DQ-BSA and decreased protease activity after Niclosamide treatments indicated the impaired lysosome function. In addition, both LC-II and P62 proteins accumulated significantly when treated by Niclosamide suggesting the late stage of autophagy was blocked. The increased pH of lysosome and release of Cathepsins from lysosome to cytosol demonstrated that Niclosamide might affect lysosome resulted from lysosomal memb...