Session Information
Date: Saturday, October 6, 2018
Session Title: Parkinson’s Disease: Clinical Trials, Pharmacology And Treatment
Session Time: 1:45pm-3:15pm
Location: Hall 3FG
Objective: To investigate the effects of metformin on the Akt/mTOR/P70S6K/4EB-P1 signaling pathway in a cellular model of Parkinson’s disease (PD).
Background: Metformin is a drug used in treatment of type 2 diabetes. The neuroprotective effect of metformin has been investigated in MPP+-treated SH-SY5Y neuroblastoma cells, which showed that metformin could activate AMPK in these cells. Some studies suggested that the neuroprotective mechanism of metformin is not strictly dependent on induction of AMPK but via inhibition of mTOR signaling. mTOR plays a key role in regulating the balance between cell survival and autophagy in response to stress signals. The role of metformin, as an AMPK activator and mTOR inhibitor, in protection of neuronal death in models of PD remain controversial.
Methods: SH-SY5Y cells were differentiated with retinoic acid into tyrosine hydroxylase-expressed neuronal cells, and treated with MPP+. The effects of metformin on cell viability and protein expression of phospho-Akt, phospho-mTOR, phospho- p70S6K, and phospho-4E-BP1 in MPP+-treated differentiated SH-SY5Y cells were investigated using an MTT assay and Western blotting, respectively.
Results: Treatment with 500 or 2000 µM of metformin alone did not affect cell viability. Pre-treatment with metformin followed by exposure to 1000 µM MPP+ significantly increased cell viability of differentiated SH-SY5Y cells compared to MPP+ alone. Compared to MPP+ treatment only, pre-treatment with metformin prior to MPP+ exposure showed significant increases in the expression of p-Akt/Akt, p-mTOR/mTOR, p- p70S6K /p70S6K, and p-4E-BP1/4E-BP1.
Conclusions: The neuroprotective effect of metformin in MPP+-treated differentiated SH-SY5Y cells is mediated via the activation of the Akt/mTOR/P70S6K/4EB-P1 signaling pathway.
References: The neuroprotective effect of metformin in MPP+-treated differentiated SH-SY5Y cells is mediated via the activation of the Akt/mTOR/P70S6K/4EB-P1 signaling pathway.
To cite this abstract in AMA style:
P. Dharmasaroja, P. Chanthammachat. The Akt/mTOR/P70S6K/4EB-P1 signaling pathway is activated by metformin in a toxin-induced cellular model of Parkinson’s disease [abstract]. Mov Disord. 2018; 33 (suppl 2). https://www.mdsabstracts.org/abstract/the-akt-mtor-p70s6k-4eb-p1-signaling-pathway-is-activated-by-metformin-in-a-toxin-induced-cellular-model-of-parkinsons-disease/. Accessed June 14, 2025.« Back to 2018 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/the-akt-mtor-p70s6k-4eb-p1-signaling-pathway-is-activated-by-metformin-in-a-toxin-induced-cellular-model-of-parkinsons-disease/