In search of the neuroprotective mechanism of thiazolidinediones in Parkinson's disease

The oral antidiabetic thiazolidinediones exert protective effects in models of Parkinson's disease and other neurological diseases. While the antidiabetic effect is due to activation of PPAR?, the mechanisms underlying the neuroprotection are more controversial. It may involve activation of PPAR? blocking inflammation and apoptosis. However, new evidence suggests an antioxidative PPAR?-independent action. Here we discuss recent data on the mode of action of TZDs in models of PD and their implication for the translation into the clinic.