Serum Response Factor Promotes Dopaminergic Neuron Survival via Activation of Beclin 1-Dependent Autophagy

Xiao Yu Cheng, Si Yue Li, Cheng Jie Mao, Mei Xia Wang, Jing Chen, Fen Wang, Guang Hui Wang, Wenbin Deng, Xiao Kang Li, Chun Feng Liu

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Serum response factor (SRF), a transcription factor highly expressed in neurons, is involved in neuronal survival and the pathogenesis of some neurodegenerative disorders. The ablation of SRF renders the midbrain dopaminergic (DA) neurons vulnerable to 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine-induced neurotoxicity, however, the underlying mechanisms remain poorly understood. Here, we report decreased SRF levels in the substantia nigra (SN) of rotenone-treated rats that was associated with the loss of tyrosine hydroxylase (TH)-positive neurons. SRF expression was also reduced in rotenone-treated PC12 cells in vitro. In addition, Srf knockdown augmented rotenone-induced toxicity in PC12 cells. In contrast, overexpression of Srf attenuated the cells’ sensitivity to rotenone and alleviated rotenone-induced α-synuclein accumulation. The protective effect of SRF was abolished when the expression of autophagy-related proteins Beclin 1 and Atg5 was suppressed. These results suggested that SRF may promote DA neuron survival by regulating autophagy, and thus serves as a critical molecule in PD progression.

Original languageEnglish (US)
Pages (from-to)288-295
Number of pages8
JournalNeuroscience
Volume371
DOIs
StatePublished - Feb 10 2018

Keywords

  • autophagy
  • Beclin 1
  • dopaminergic neuron
  • Parkinson's disease
  • serum response factor

ASJC Scopus subject areas

  • Neuroscience(all)

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    Cheng, X. Y., Li, S. Y., Mao, C. J., Wang, M. X., Chen, J., Wang, F., Wang, G. H., Deng, W., Li, X. K., & Liu, C. F. (2018). Serum Response Factor Promotes Dopaminergic Neuron Survival via Activation of Beclin 1-Dependent Autophagy. Neuroscience, 371, 288-295. https://doi.org/10.1016/j.neuroscience.2017.11.040