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. 2017 Mar 9;18(3):592. doi: 10.3390/ijms18030592

Figure 1.

Figure 1

Pathophysiological roles of adiponectin in Alzheimer’s disease (AD). Schematic outline of neuronal adiponectin signaling in the normal brain (A); and adiponectin-deficient brain (B). Under physiological conditions, adiponectin binds to its receptor and triggers phosphorylation of AMPK which inhibits IRS-1 phosphorylation at serine residues. This increases insulin-mediated IRS-1 phosphorylation at tyrosine residues and promotes downstream Akt-mediated GSK3 inhibition. Inhibition of GSK3 slows down phosphorylation of Tau and APP metabolism. In AD, chronic adiponectin deficiency leads to an increase of IRS-1 phosphorylation at serine residues (e.g., Serine 616). This causes reduced pIRS-1Tyr and results in GSK3 activation. Activated GSK3 enhances Tau phosphorylation and Aβ production in neurons. Arrows denote promotion, T-bars denote inhibition.