1. Academic Validation
  2. Sodium butyrate causes α-synuclein degradation by an Atg5-dependent and PI3K/Akt/mTOR-related autophagy pathway

Sodium butyrate causes α-synuclein degradation by an Atg5-dependent and PI3K/Akt/mTOR-related autophagy pathway

  • Exp Cell Res. 2020 Feb 1;387(1):111772. doi: 10.1016/j.yexcr.2019.111772.
Chen-Meng Qiao 1 Meng-Fei Sun 1 Xue-Bing Jia 1 Yun Shi 1 Bo-Ping Zhang 1 Zhi-Lan Zhou 1 Li-Ping Zhao 1 Chun Cui 1 Yan-Qin Shen 2
Affiliations

Affiliations

  • 1 Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China.
  • 2 Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China. Electronic address: [email protected].
Abstract

Aggregation of α-synuclein is central to the pathogenesis of Parkinson's disease (PD). However, these α-synuclein inclusions are not only present in brain, but also in gut. Enteroendocrine cells (EECs), which are directly exposed to the gut lumen, can express α-synuclein and directly connect to α-Synuclein-containing nerves. Dysbiosis of gut microbiota and microbial metabolite short-chain fatty acids (SCFAs) has been implicated as a driver for PD. Butyrate is an SCFA produced by the gut microbiota. Our aim was to demonstrate how α-synuclein expression in EECs responds to butyrate stimulation. Interestingly, we found that sodium butyrate (NaB) increases α-synuclein mRNA expression, enhances Atg5-mediated Autophagy (increased LC3B-II and decreased SQSTM1 (also known as p62) expression) in murine neuroendocrine STC-1 cells. Further, α-synuclein mRNA was decreased by the inhibition of Autophagy by using inhibitor bafilomycin A1 or by silencing Atg5 with siRNA. Moreover, the PI3K/Akt/mTOR pathway was significantly inhibited and cell Apoptosis was activated by NaB. Conditioned media from NaB-stimulated STC-1 cells induced inflammation in SH-SY5Y cells. Collectively, NaB causes α-synuclein degradation by an Atg5-dependent and PI3K/Akt/mTOR-related Autophagy pathway.

Keywords

Apoptosis; Autophagy; Inflammation; Parkinson's disease; Sodium butyrate; α-Synuclein.

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