Inhibition of STAT Transcription Factor Attenuates MPP⁺-induced Neurotoxicity

Inhibition of STAT Transcription Factor Attenuates MPP⁺-induced Neurotoxicity

Background: The most prominent pathological features of Parkinson's disease (PD) are diminished substantia nigra (SN), which is part of the output component of the basal ganglia, the severe death of dopaminergic neuronal cell and the accumulation of a synuclein (αSYN). However, the mechanism by which αSYN causes toxicity and contributes to neuronal death remains unclear. Methods: The aim of this study was to investigate the effect of αSYN/STAT oligodeoxynucleotide (ODN), which simultaneously suppresses STAT transcription factors and αSYN mRNA expression in an in vitro Parkinson's disease model. Results: Synthetic αSYN/STAT ODN effectively inhibits 1-Methyl-4-phenylpyridinium (MPP⁺) induced STAT phosphorylation and αSYN expression. αSYN/STAT ODN attenuated MPP⁺ to mimic PD model in vitro. MPP⁺ induced the secretion of TNF-α/IL-6, inhibited cell viability and induced apoptosis while these effects could be rescued by αSYN/STAT ODN. Conclusion: Therefore, synthetic αSYN/STAT ODN has substantial therapeutic feasibility for the treatment of neurodegenerative diseases.