Fig.2.

Molecular pathways recruited following proteasome inhibition. At high, lethal doses (upper panel), proteasome inhibitors activate multiple downstream toxic pathways that together converge in inducing neuronal death. At lower, sub-lethal doses (lower panel), proteasome inhibitors can lead to a neuroprotective response, characterized by activation of anti-oxidant pathways and clearance of α-synuclein oligomers into larger, potentially less toxic fibrils. Lactacystin is exemplified as a typical proteasome inhibitor, although similar effects are observed with structurally distinct inhibitors. See text for details. ER endoplasmic reticulum, ROS reactive oxygen species.