Table 2 Beneficial effects of the chemical inducers of autophagy in models of lysosomal storage disorders
Autophagy inducerMechanism of autophagy inductionLSDBeneficial effects in LSD models
mTOR-DEPENDENT AUTOPHAGY INDUCER
Rapamycin [42]Inhibition of mTORC1 [42]NPC1Rescue of autophagic flux and improvement in cell viability in mutant Npc1 MEFs [73], mouse neurons with Npc1 knockdown [73] and NPC1 patient iPSC-derived neuronal and hepatic cells [74]
NPBReduction in mitochondrial ROS and lipid droplets, and induction of lysosomal exocytosis in NPB patient B lymphocytes [148]
PDReduction in muscle glycogen in Gaa-deficient mice when treated together with recombinant human GAA [167]; Improved autophagic flux and GAA maturation in Pompe disease patient myotubes [117]
GDImprovement in lifespan and locomotor activity in GD Drosophila model [97]
mTOR-INDEPENDENT AUTOPHAGY INDUCER
Trehalose [44]Inhibition of SLC2A glucose transporters [145]; Activation of TFEB by Akt inhibition [144]NPC1Rescue of autophagic flux and improvement in cell viability in NPC1 patient iPSC-derived neurons [74]
CLN3Clearance of ceroid lipopigment deposits in CLN3 patient fibroblasts, and attenuation of neuropathology and extension of lifespan in Cln3-deficient mice [144]
Carbamazepine [35]Reduction in inositol and IP3 levels [35]NPC1Rescue of autophagic flux and improvement in cell viability in NPC1 patient iPSC-derived neurons and hepatic cells [74]
Lithium [35]Inhibition of IMPase and reduction in inositol and IP3 levels [35]NPC1Rescue of autophagic flux in mutant Npc1 MEFs [73]
CLN3Rescue of autophagic flux and improvement in cell viability in mutant Cln3 cerebellar cells [146]
L-690,330 [35]Inhibition of IMPase and reduction in inositol and IP3 levels [35]CLN3Rescue of autophagic flux and improvement in cell viability in mutant Cln3 cerebellar cells [146]
Verapamil [36]Inhibition of L-type Ca2+ channel and reduction in cytosolic Ca2+ [36]NPC1Rescue of autophagic flux and improvement in cell viability in NPC1 patient iPSC-derived neurons [74]
BRD2716, BRD5631, BRD34009 [142]UnknownNPC1Rescue of autophagic flux and improvement in cell viability in NPC1 patient iPSC-derived neurons [142]
  • Abbreviations: CLN, ceroid lipofuscinosis neuronal disease; GD, Gaucher disease; IMPase, inositol monophosphatase; IP3, inositol 1,4,5-trisphosphate; iPSC, induced pluripotent stem cells; LSD, lysosomal storage disorder; mTORC1, mechanistic target of rapamycin complex I; NPB, Niemann–Pick type B disease; NPC1, Niemann–Pick type C1 disease; PD, Pompe disease; SLC2A, Solute carrier 2A; TFEB, Transcription factor EB.