Expression of FasL and its interaction with Fas are mediated by c-Jun N-terminal kinase (JNK) pathway in 6-OHDA-induced rat model of Parkinson disease

Abstract

Our previous studies and those of others have strongly suggested that c-Jun N-terminal kinase (JNK) signaling pathway plays a critical role in 6-hydroxydopamine (6-OHDA)-induced dopaminergic neuron injury in the substantia nigra. However, the downstream mechanism that accounts for the proapoptotic actions of JNK in 6-OHDA lesion remains to be investigated in detail. Fas, a member of the tumor necrosis factor receptor family with proapoptotic functions, was reported to be elevated within the striatum and substantia nigra pars compacta (SNc) of Parkinson's disease (PD) patients. In the present study, we examined the changes in the protein level of Fas ligand (FasL) and its interaction with Fas in a rat model of PD. We demonstrate that the expression of FasL and not Fas was increased after 6-OHDA lesion; additionally, the interaction of FasL and Fas was increased due to 6-OHDA lesion. This indicates that the 6-OHDA-induced activation of Fas signaling pathway is mediated by JNK and that FasL may be a promising target in the therapeutic approach for PD patients.