Neuroprotection by dipeptidyl-peptidase-4 inhibitors and glucagon-like peptide-1 analogs via the modulation of AKT-signaling pathway in Alzheimer’s disease

Figure 1 Several modulator molecules linked to the phosphoinositide-3 kinase/AKT/mammalian/mechanistic target of rapamycin signaling in an extracellular growth-factor response are demonstrated. Example molecules known to act on the glucagon-like peptide-1 (GLP1)-receptor/adenosine monophosphate-activated protein kinase (AMPK)/mammalian/mechanistic target of rapamycin (mTOR) signaling pathway are also shown. Note that some critical events such as immune activation and/or cytokine-induction have been omitted for clarity. Arrowhead means stimulation whereas hammerhead represents inhibition. PI3K: Phosphoinositide-3 kinase; PKA: Protein kinase A; PTEN: Phosphatase and tensin homologue deleted on chromosome 10; DPP4: Dipeptidyl-peptidase-4; GSK3: Glycogen synthase kinase 3; MAPK: Mitogen-activated protein kinase; S6K: S6 kinase; AC: Adenylate cyclase; Gs: Stimulatory G-protein; elF-4E: Eukaryotic translation initiation factor 4E; TSP1: Thrombospondin-1; VEGF: Vascular endothelial growth factor; NOS: Nitric oxide synthase; IKK: I kappa B kinase; NF-kB: Nuclear factor-kappa B; HDM2: Human double minute 2; HIF-1a: Hypoxia inducible factor 1-alpha.

Figure 2 Implication of decreased dipeptidyl-peptidase-4 activity, increased Glucagon-like peptide-1, increased Glucagon-like peptide-1-receptor agonists, and decreased mammalian/mechanistic target of rapamycin activity for the neuroprotection. Arrowhead means stimulation whereas hammerhead represents inhibition. Note that some critical pathways have been omitted for clarity. GLP1: Glucagon-like peptide-1; mTOR: Mammalian/mechanistic target of rapamycin; DPP4: Dipeptidyl-peptidase-4.

Figure 3 Simplified diagrams indicating the biochemical properties of several natural products are shown. Several herbs and/or their ingredients may contribute to the neuroprotection against the progression of Alzheimer’s disease. Hammerhead represents inhibition. DPP4: Dipeptidyl-peptidase-4; GLP1: Glucagon-like peptide-1; mTOR: Mammalian/mechanistic target of rapamycin.