Elevated cytosolic DA levels have been shown to result in increased neurotoxicity in cellular models of PD (Mosharov et al., 2009). In a new study published in the Journal of Neuroscience Research, Gomez-Santos and colleagues confirm these findings in PC12 cells. They show that extracellular application of DA leads to a dose-dependent decrease in cell viability and to an increase in alpha-synuclein expression mediated at least in part by activation of p38. They also show that exposure to DA increases the number of autophagic vacuoles and that treatment with 3-MA, an autophagy inhibitor, was protective against DA-mediate cell death. Treatment with nomifensine, a DAT inhibitor, and with antioxidants was also protective. It would be interesting to test whether treatment with nomifensine and antioxidants prevents the increase in alpha-synuclein expression and to examine by what mechanism p38 and autophagy inhibition result in a decrease in alpha-synuclein expression as reported in this study.
Elevated cytosolic DA levels have been shown to result in increased neurotoxicity in cellular models of PD (Mosharov et al., 2009). In a new study published in the Journal of Neuroscience Research, Gomez-Santos and colleagues confirm these findings in PC12 cells. They show that extracellular application of DA leads to a dose-dependent decrease in cell viability and to an increase in alpha-synuclein expression mediated at least in part by activation of p38. They also show that exposure to DA increases the number of autophagic vacuoles and that treatment with 3-MA, an autophagy inhibitor, was protective against DA-mediate cell death. Treatment with nomifensine, a DAT inhibitor, and with antioxidants was also protective. It would be interesting to test whether treatment with nomifensine and antioxidants prevents the increase in alpha-synuclein expression and to examine by what mechanism p38 and autophagy inhibition result in a decrease in alpha-synuclein expression as reported in this study.