Figure 32

Proposed mechanism of action of active site-specific chaperones (ASSCs): A: During synthesis of a wild-type lysosomal enzyme, cells assemble amino acids in a correctly folded tertiary structure. Molecular chaperones are naturally occurring molecules that assist in protein folding. B: In contrast, mutant misfolded lysosomal enzymes are unstable and retained in the endoplasmic reticulum (ER) where they may not meet quality control and are prone to endoplasmic reticulum-associated degradation (ERAD). C: ASSCs are designed to stabilize and rescue misfolded lysosomal enzymes, leading to reduced ER retention or accumulation, and enhanced trafficking to the Golgi apparatus and the lysosome where they dissociate from the enzyme.