Figure 7.

Proposed protective mechanisms of PEDs. Red and blue lines indicate activation of stress response signaling pathways by D1 and D3, respectively. D1 activates both the ARE system and the HSE system, inducing phase 2 enzymes and HSPs, and thus protecting neurons against oxidative stress and ER stress. By also inducing HSPs, D1 reduces protein misfolding, alleviates ER stress, and affords significant resistance to neuronal cells. Compound D3 is a weaker activator of these pathways. PEDs = proelectrophilic drugs; ARE = antioxidant response element; HSE = heat-shock factor response element; HSP = heat-shock protein; ER = endoplasmic reticulum.