1. BDNF and insulin signaling pathways activated by phytochemicals.
BDNF and insulin signaling pathways activated by phytochemicals. Several phytochemicals, including those indicated, have been shown to activate the BDNF and/or insulin signaling pathways. Receptors for BDNF and insulin are similar in structure and couple to similar downstream signaling pathways. The BDNF receptor TrkB and the insulin receptor have a tyrosine kinase domain in their cytoplasmic region. Binding of ligand results in receptor dimerization and trans-autophosphorylation (p) of the receptors that then recruits adaptor proteins and activates several downstream proteins kinases as indicated. A prominent transcription factor activated by BDNF is CREB, which induces the expression of genes encoding proteins involved in synaptic plasticity (e.g., Arc), cellular energy metabolism (e.g., PGC-1α, which induces mitochondrial biogenesis), and stress resistance (e.g., the DNA repair enzyme APE1). Activation of both TrkB and the insulin receptor can also activate the PI3K (p85–p110) Akt kinase signaling resulting in the inhibition of GSK-3β and FOXO, thereby protecting neurons against degeneration. Activation of the Grb/SOS, Ras, Raf, MEK, and ERK pathways can enhance cellular stress resistance and increase insulin sensitivity. Akt, Akt kinase; APE1, apurinic/apyrimidinic endonuclease 1; CaMK, calcium/calmodulin-dependent kinase; Grb2, growth factor receptor bound protein 2; MAPKK, mitogen-activated protein kinase kinase; PGC-1α, PPARγ coactivator 1α; PIP2, phosphatidylinositol bisphosphate; PIP3, phosphatidylinositol trisphosphate; SOS, son of sevenless homolog 1.
Jaewon Lee et al. Pharmacol Rev 2014;66:
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