Research Paper Volume 14, Issue 3 pp 1233—1252

PERK activation by SB202190 ameliorates amyloidogenesis via the TFEB-induced autophagy-lysosomal pathway


Figure 7. Schematic overview of the mechanisms by which SB202190 ameliorates amyloidogenesis via PERK activation. PERK, a tethering molecule of the mitochondrial-associated ER membrane (MAM), is activated by mitochondrial ROS (mtROS) in response to treatment with the PERK activator (SB202190). Activated PERK leads to increase in cytosolic Ca2+ levels and subsequently promotes the translocation of TEFB into the nucleus via the calcineurin-dependent dephosphorylation TFEB, which culminates in the increased transcription of autophagy-lysosome related genes. The increase of autophagy-lysosomal pathway (ALP) by PERK activation enhances the degradation of misfolded proteins that accumulate in neurodegenerative disorders. Therefore, the PERK-TFEB-ALP pathway activated by SB202190 suggests the novel target for ameliorating amyloidogenesis.