Research ReportMG132 enhances neurite outgrowth in neurons overexpressing mutant TAR DNA-binding protein-43 via increase of HO-1

In patients with amyotrophic lateral sclerosis (ALS), various mutations were identified in TAR DNA-binding protein-43 (TDP-43). In the present study, we found that mutant TDP-43 inhibited the neurite outgrowth. Subsequently, we tested the effect of MG132 on the mutant TDP-43 cell lines. Non-toxic doses of MG132 promoted neurite extension and decreased the level of thiobarbituric acid-reactive substances (TBARS). Heme oxygenase-1 (HO-1) known as antioxidase was restored by MG132. Conversely, Zinc protoporphyrin IX (ZnPP IX), which is an inhibitor of heme oxygenase, inhibited neurite outgrowth induced by MG132. It was well known that HO-1 was regulated by nuclear factor E2-related factor 2 (Nrf2). However, MG132 increased the expression of HO-1 independent of the Nrf2 pathway.

Research highlights► Mutant TDP-43 inhibited neurite outgrowth. ► Non-toxic MG132 promoted the neurite outgrowth in the mutant TDP-43 cell lines. ► Non-toxic MG132 enhanced the antioxidative capacity independent of Nrf2 pathway.