Figure 2.

Role of ERs and ERRs in AD pathogenesis. (A) ERα and ERβ are involved in Aβ clearance through transcriptional activation of the neprilysin (NEP) gene. ERβ also activates the autophagy machinery to remove Aβ. In addition, it plays a neuroprotective role by regulating neuronal mitochondrial health. (B) mERα/β inhibit Aβ-induced neurotoxicity by inactivating a channel, VDAC1, at the plasma membrane. (C) ERRα, probably with PGC-1α, suppresses the expression of BACE1 and the kinase activity of GSK-3β, leading to Aβ clearance and tau phosphorylation (P-tau).