Autophagy defects in NPC1 disease and the bypass mechanism of autophagosome maturation for restoring autophagic flux Autophagy defects in NPC1 disease.

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Autophagy defects in NPC1 disease and the bypass mechanism of autophagosome maturation for restoring autophagic flux Autophagy defects in NPC1 disease and the bypass mechanism of autophagosome maturation for restoring autophagic flux Mutant NPC1 protein prevents cholesterol efflux from the endo-lysosomal compartments and impairs autophagosome maturation in the multi-step route due to failure in the SNARE machinery. Induction of autophagy by chemical inducers bypasses this block and restores autophagic flux via direct autophagosome–lysosome fusion. A combinatorial treatment strategy is shown with cholesterol depletion agents. The green arrows indicate therapeutic effects of autophagy induction and cholesterol depletion. Elena Seranova et al. Essays Biochem. 2017;61:733-749 ©2017 by Portland Press Ltd