Synphilin-1 exhibits trophic and protective effects against Rotenone toxicity

X. Li, Z. Liu, K. Tamashiro, B. Shi, D. D. Rudnicki, C. A. Ross, T. H. Moran, W. W. Smith

Research output: Contribution to journalArticle

Abstract

Synphilin-1 is a cytoplasmic protein with unclear function. Synphilin-1 has been identified as an interaction partner of α-synuclein. The interaction between synphilin-1 and α-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.

Original languageEnglish (US)
Pages (from-to)455-462
Number of pages8
JournalNeuroscience
Volume165
Issue number2
DOIs
StatePublished - Jan 20 2010

Keywords

  • ERK1/2
  • N1E-115 neuroblastoma cells
  • Parkinson's disease
  • caspase-3
  • neuroprotection

ASJC Scopus subject areas

  • Neuroscience(all)

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