Fig. 1: Insulin signaling pathway was found to be associated with cerebrovascular pathologies in AD including inflammation, BBB disruption, and Aβ accumulation. | npj Systems Biology and Applications

Fig. 1: Insulin signaling pathway was found to be associated with cerebrovascular pathologies in AD including inflammation, BBB disruption, and Aβ accumulation.

From: Mapping the dynamics of insulin-responsive pathways in the blood–brain barrier endothelium using time-series transcriptomics data

Fig. 1

Inflammation: PI3K/Akt pathway mediates eNOS activation10 which could inhibit VCAM-1 expression11 in endothelial cells. BBB disruption: Inhibition of GSK3β was shown to promote tight junction stability in BBB8 and insulin enhanced the BBB integrity via PI3K/Akt/GSK3β pathway48. Aβ accumulation: Insulin exposure promoted Aβ degradation via an increase in insulin-degrading enzyme (IDE) expression in astrocytes, via activation of the ERK-mediated pathway9. In neurons, Aβ exposure was shown to induce insulin resistance by inhibiting IRS166, PDK-dependent Akt activation67, and activating p38 pathway68. Preliminary data from our lab suggests that Aβ could have a similar effect on these pathways in BBB endothelial cells.

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