title: Autophagic modulation by rosuvastatin prevents rotenone-induced neurotoxicity in an in vitro model of Parkinson's disease.
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 α-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 α-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 ɑ-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.
authors.affiliation: Department of Neurology, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Republic of Korea; Department of Family Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Seo Young
authors.initials: SY
authors.lastname: Kang
authors.affiliation: Natural Medicine Center, Korea Institute of Science and Technology, Gangneung 210-340, Republic of Korea; School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Sang-Bin
authors.initials: SB
authors.lastname: Lee
authors.affiliation: Department of Neurology, Gangnung Asan Hospital, Biomedical Research Center, Gangneung, Republic of Korea.
authors.forename: Hee Ju
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Neurology, Hanyang University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hee-Tae
authors.initials: HT
authors.lastname: Kim
authors.affiliation: Natural Medicine Center, Korea Institute of Science and Technology, Gangneung 210-340, Republic of Korea. Electronic address: hoyang@kist.re.kr.
authors.forename: Hyun Ok
authors.initials: HO
authors.lastname: Yang
authors.affiliation: Department of Neurology, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Republic of Korea. Electronic address: neveu@gnah.co.kr.
authors.forename: Wooyoung
authors.initials: W
authors.lastname: Jang
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D010300:Parkinson Disease / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D000068718:Rosuvastatin Calcium / Q000494:pharmacology*; D012402:Rotenone / Q000633:toxicity*; D051844:alpha-Synuclein / Q000378:metabolism
chemical_list: D000071186:Beclin-1; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D051844:alpha-Synuclein; D012402:Rotenone; D000068718:Rosuvastatin Calcium; D000263:Adenylate Kinase
keywords: Autophagy; Neuroprotection; Parkinson’s disease; Rosuvastatin