| First Author | Li X | Year | 2010 |
| Journal | Neuroscience | Volume | 165 |
| Issue | 2 | Pages | 455-62 |
| PubMed ID | 19857556 | Mgi Jnum | J:158193 |
| Mgi Id | MGI:4438267 | Doi | 10.1016/j.neuroscience.2009.10.042 |
| Citation | Li X, et al. (2010) Synphilin-1 exhibits trophic and protective effects against Rotenone toxicity. Neuroscience 165(2):455-62 |
| abstractText | Synphilin-1 is a cytoplasmic protein with unclear function. Synphilin-1 has been identified as an interaction partner of alpha-synuclein. The interaction between synphilin-1 and alpha-synuclein has implications in Parkinson's disease. In this study, we stably overexpressed human synphilin-1 in mouse N1E-115 neuroblastoma cells. We found that overexpression of synphilin-1 shortened cell growth doubling time and increased neurite outgrowth. Knockdown of endogenous synphilin-1 caused neuronal toxicity and shortened neurite outgrowth. We further found that synphilin-1 increased activation of the extracellular signal-regulated kinases (ERK1/2) and mediated neurite outgrowth. Rotenone, mitochondrial complex I inhibitor, has been shown previously to induce dopaminergic neurodegeneration and Parkinsonism in rats and Drosophila. We found that Rotenone induced apoptotic cell death in N1E-115 cells via caspase-3 activation and poly (ADP-ribose) polymerase (PARP) cleavage. Overexpression of synphilin-1 significantly reduced Rotenone-induced cell death, caspase-3 activation and PARP cleavage. The results indicate that synphilin-1 displays trophic and protective effects in vitro, suggesting that synphilin-1 may play a protective role in Parkinson's disease (PD) pathogenesis and may lead to a potential therapeutic target for PD intervention. |
