Fig. 3

The main intracellular targets involved in the neuroprotective effects of phytochemicals. Most of the phytochemicals with neuroprotective activity seem to converge in the modulation of stress response pathways. For example, phytochemicals can interact directly with Nrf2, allowing the expression of phase II detoxifier genes. The kinases p38, ERK and JNK are also modulated by phytochemicals, regulating both survival and death pathways in response to different stresses. Activation of SIRT1 can regulate FoxO, which modulate genes that encode antioxidant and other stress-response proteins. FoxO is also regulated by ERK in response to a variety of stimuli, including IO&NS and phytochemicals. ERK activation often leads to the activation of Nrf2. Phytochemicals and/or activated SIRT1can also inhibit NF-κB, reducing the expression of inflammatory mediators