Fig. 3

Distinctive hypothetical pathways through which impairment of GCase occurs and therapies targeting these pathways. a: GCase failure to escape the ER; b GCase failure to link with LIMP2 transporter; c misfolded and degraded GCase; d GCase failure to escape Golgi; e inactive GCase due to the mutation at the active site; f Altered GCase function due to the defective saposin C. The targeted therapies are (1) Gene therapy: direct replacement of mutant DNA with the correct DNA via viral infections; (2) Chaperone therapy to refold and stabilize misfolded proteins; (3) Histone deacetylase inhibitors that inhibit the response of unfolded protein; (4) Enzyme replacement therapy: substituting the dysfunctional enzyme with the recombinant enzyme in the targeted lysosome; and (5) Substrate replacement therapy: diminishing the accumulation of substrate independent of the enzyme level