Glycogen synthase kinase-3β (GSK-3β) is an attractive therapeutic target for human diseases, such as diabetes, cancer, neurodegenerative diseases, and inflammation.
Recent studies have identified GSK-3β as a potential therapeutic target in Alzheimer´s disease, bipolar disorder, stroke, more than 15 types of cancer, and diabetes.
Consistent with its critical roles in normal cells, abnormalities in GSK-3β activity have been implicated in diabetes, heart disease, Parkinson disease, and Alzheimer's disease.
Intrahippocampal TDZD-8 blocked tau hyperphosphorylation and normalized hippocampus-dependent memory in db/db mice, suggesting that pathological synergy between diabetes and Alzheimer's disease may involve glucocorticoid-mediated activation of GSK3β.
These studies demonstrate that EPO is an effective neuroprotective agent in the context of diabetes-associated cognitive dysfunction and show that this effect involves the PI3K/Akt/GSK-3β pathway.
To determine whether GSK3β affects nutrient-induced changes in autophagy and AMPK activity, we used a primary human aortic endothelial cell (HAEC) model of type 2 diabetes that we had previously characterized with impaired AMPK activity and autophagy [Weikel et al.(2015) Am.J. Phys.Cell Physiol.308: , C249-C263].
These data suggested that phospho-GSK-3β is involved in the high-glucose-mediated increase of SREBP-1 expression and triglyceride content in renal tubular cells in diabetes.