Geniposide Attenuates the Phosphorylation of Tau Protein in Cellular and Insulin-deficient APP/PS1 Transgenic Mouse Model of Alzheimer's Disease

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Abstract

Our previous studies have shown that geniposide plays an essential role in glucose-stimulated insulin secretion from pancreatic β cells and also regulates the metabolism of Aβ and its deposition in neurons. In this study, we reported that insulin deficiency induced significant increase of tau phosphorylation. Administration of geniposide for 4 weeks significantly decreased the phosphorylated level of tau and the acceleration of GSK-3β phosphorylation in the brain of APP/PS1 transgenic mice induced by insulin deficiency. We also observed that geniposide decreased the phosphorylation of tau protein directly and increased the phosphorylation of Akt in primary cultured cortical neurons. Furthermore, geniposide enhanced the role of insulin on the phosphorylation of Akt, GSK-3β, and tau in primary cultured cortical neurons. And these effects of geniposide in cortical neurons could be prevented by preincubation with LY294002, an inhibitor of PI3K. Taken together, our findings provide a mechanistic and perhaps a foundational link between diabetes and Alzheimer's disease and are consistent with the notion that geniposide might play an essential role on the phosphorylation of tau protein via enhancing insulin signaling and may convey a therapeutic benefit in Alzheimer's disease.

Geniposide attenuates the phosphorylation of tau protein by potentiating the insulin signaling in cellular and APP/PS1 transgenic mouse model of Alzheimer's disease.

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