Figure 8

Schematic diagram of PTP1B in IFN-γ-induced neuroinflammation and 6-OHDA-induced neuronal death. IFN-γ could increase PTP1B expression and further modulate downstream cascade, including the upregulation of proinflammatory cytokines, such as iNOS, COX-2, and NF-κB. Treatment of 6-OHDA could also affect PTP1B and its downstream neuroprotection-related pathway, including the downregulation of p-CREB, GRP-78, and BDNF and upregulation of p-eIF2. Our study revealed that the PTP1B inhibition by suramin could reverse IFN-γ-induced upregulation of iNOS and COX-2 protein expression. Moreover, suramin could modulate M2 type microglia-related protein and increase arginase-1 and Ym-1 protein expression. PTP1B inhibition also reversed the 6-OHDA-induced downregulation of p-CREB and BDNF protein expression. In the anti-ER stress section, suramin further enhanced 6-OHDA-induced upregulation of p-eIF2 expression and reversed 6-OHDA-induced downregulation of GRP-78 expression. The effect of suramin significantly protected dopamine neurons against damage.