Autophagic modulation by rosuvastatin prevents rotenone-induced neurotoxicity in an in vitro model of Parkinson's disease

Authors
Kang, Seo YoungLee, Sang-BinKim, Hee JuKim, Hee-TaeYang, Hyun OkJang, Wooyoung
Issue Date
2017-03-06
Publisher
ELSEVIER IRELAND LTD
Citation
NEUROSCIENCE LETTERS, v.642, pp.20 - 26
Abstract
Statins have been reported to have neuroprotective effects through anti-oxidant, anti-apoptotic, and anti-inflammatory mechanisms, and statin can also modulate autophagic signaling in an oxygen toxicity models. Therefore, we investigated the effects of statin on autophagy markers and evaluated the neuroprotective effect of rosuvastatin against rotenone-induced neurotoxicity. As an in vitro model of Parkinson's disease(PD) we adopted the rotenone-induced neurotoxicity model in SH-SY5Y cells. Cell viability was measured using the MTT assay, and to detect the expression of LC3 and a.synuclein, immunofluorescence analysis was performed. Intracellular signaling proteins associated with autophagy were explored via immunoblotting. Treatment with rosuvastatin alone increased the levels of mTOR-independent/upstream autophagy markers, including Beclin-1 and AMPK. Rotenone treatment of SH-SY5Y cells reduced their viability and ce-synuclein expression; simultaneous exposure to rosuvastatin significantly restored these parameters. Rotenone enhanced mTOR expression and suppressed Beclin-1 expression, indicating suppression of the autophagic system. However, combined treatment with rosuvastatin also restored the Beclin-1 expression and decreased mTOR expression. We demonstrated the neuroprotective effect of statin in SH-SY5Y cells against rotenone-induced neurotoxicity, as well as the modulation of a-synuclein expression. The neuroprotective mechanism is likely to be associated with enhanced autophagy. The neuroprotective effect of statin on rotenone-induced dopaminergic neurotoxicity with modulation of autophagy provides a new therapeutic strategy for the treatment of PD. (C) 2017 Elsevier B.V. All rights reserved.
Keywords
PATHOLOGICAL ALPHA-SYNUCLEIN; MESENCHYMAL STEM-CELLS; MOLECULAR-MECHANISMS; SIGNALING PATHWAY; NEURODEGENERATION; ATORVASTATIN; PATHOGENESIS; SIMVASTATIN; INHIBITION; DISCOVERY; PATHOLOGICAL ALPHA-SYNUCLEIN; MESENCHYMAL STEM-CELLS; MOLECULAR-MECHANISMS; SIGNALING PATHWAY; NEURODEGENERATION; ATORVASTATIN; PATHOGENESIS; SIMVASTATIN; INHIBITION; DISCOVERY; Rosuvastatin; Parkinson' s disease; Autophagy; Neuroprotection
ISSN
0304-3940
URI
https://pubs.kist.re.kr/handle/201004/122960
DOI
10.1016/j.neulet.2017.01.063
Appears in Collections:
KIST Article > 2017
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