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. Epub 2019 Dec 10.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Autophagy / drug effects
  • Autophagy-Related Protein 5 / metabolism*
  • Butyric Acid / pharmacology*
  • Cell Line
  • Mice
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RNA, Messenger / metabolism
  • Signal Transduction / drug effects*
  • TOR Serine-Threonine Kinases / metabolism*
  • alpha-Synuclein / metabolism*


  • Atg5 protein, mouse
  • Autophagy-Related Protein 5
  • RNA, Messenger
  • alpha-Synuclein
  • Butyric Acid
  • mTOR protein, mouse
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases