Session Information
Date: Thursday, June 23, 2016
Session Title: Neuropharmacology
Session Time: 12:00pm-1:30pm
Location: Exhibit Hall located in Hall B, Level 2
Objective: We investigated effects of statin on autophagy markers and evaluated the neuroprotective effect of rosuvastatin from rotenone induced neurotoxicity.
Background: Recently, autophagy pathway is regarded as important mechanism in pathogenesis of Parkinson’s disease (PD) and modulation of autophagy may be a novel strategy for the treatment of PD. Statin has been reported to have neuroprotective effect through anti-oxidant, anti-apoptotic, and anti-inflammatory mechanism and statin could also modulate autophagy signaling in various models.
Methods: As an in vitro model of PD, We adapted the rotenone-induced neurotoxicity model in SH-SY5Y cells. We measured cell viability using an MTT assay, Annexin V/propidium iodide assay, and intracellular reactive oxygen species levels. To detect the expression of LC3 and α-synuclein, immnunoflorescence analysis was performed. Intracellular signaling proteins associated with autophagy were explored by immunoblot analysis.
Results: Rosuvastatin mono-treatment increased levels of mTOR independent/upstream autophagy markers, including beclin-1, AMPK, and ULK-1. Rotenone treatment of SH-SY5Y cells reduced their viability, increased reactive oxygen species levels, induced apoptosis and α-synuclein expression; simultaneous exposure to rosuvastatin significantly restored these effects. Rotenone enhanced mTOR expression and suppressed beclin-1 expression, indicating suppression of autophagic system. However, combined treatment with rosuvastatin also restored the beclin-1 expression and decreased mTOR expression.
Conclusions: We demonstrated the neuroprotective effect of statin in SH-SY5Y cells against rotenone-induced neurotoxicity and modulation of α-synuclein expression. The mechanism of neuroprotection is likely to be associated with enhanced autophagy. The neuroprotective effect of statin on rotenone-induced dopaminergic neurotoxicity with autophagy modulation provides a new therapeutic strategy for the treatment of PD.
To cite this abstract in AMA style:
W. Jang. Autophagic modulation by rosuvastatin prevent rotenone induced neurotoxicity as an in vitro model of Parkinson’s disease [abstract]. Mov Disord. 2016; 31 (suppl 2). https://www.mdsabstracts.org/abstract/autophagic-modulation-by-rosuvastatin-prevent-rotenone-induced-neurotoxicity-as-an-in-vitro-model-of-parkinsons-disease/. Accessed September 21, 2023.« Back to 2016 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/autophagic-modulation-by-rosuvastatin-prevent-rotenone-induced-neurotoxicity-as-an-in-vitro-model-of-parkinsons-disease/