Molecular and biochemical trajectories from diabetes to Alzheimer’s disease: A critical appraisal

Figure 3 Diagrammatic representation of molecular orchestra downstream of insulin receptor. IRs activation leads to downstream PI3K signaling pathway with Akt as a central hub which diverges into three main branches including FOXO, GSK3β and mTOR. Akt inhibition leads to activated FOXO and GSK3β response while inactivated mTOR response. FOXO activation leads to cellular stress response, mTOR dysfunction leads to loss of translational control and altered cognition while GSK3β activation leads to Aβ and tau production. T2D: Type 2 diabetes; PI3K: Phosphatidylinositide 3-kinases; Aβ: Amyloid beta; GSK3β: Glycogen synthase kinase 3 beta; FOXO: Forkhead box O; mTOR: Mammalian target of rapamycin; LTD: Long term depression.