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Proposed model of the mechanism of action trehalose, and its analogs: trehalose, melibiose and lactulose act on lysosomes inducing a transient lysosomal membrane permeability. This causes Ca2+ leaks which activates the phosphatase PPP3/calcineurin. PPP3 specifically de-phosphorylates TFEB inducing its activation and nuclear translocation to activate autophagy and lysophagy with removal of damaged lysosomes and in parallel (if present) misfolded protein aggregates.
