title: Neurochemical effects of the R form of α-lipoic acid and its neuroprotective mechanism in cellular models of Parkinson's disease.
abstract: Parkinson's disease (PD) is a common neurodegenerative disease. This study aimed to investigate the effects of the R form of α-lipoic acid (RLA) in cellular models of PD induced by 6-hydroxydopamine (6-OHDA) or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
  
  
  
  Cell viability and apoptosis were detected using CCK8 and Annexin V-FITC assays, respectively. Intracellular reactive oxygen species (ROS) were detected by fluorescence staining. ELISA assays were performed to detect the levels of dopamine and α-synuclein. To evaluate the effects of RLA on mitochondrial function, cytotoxicity, ATP levels, and mitochondrial gene expression were assayed. Additionally, the expression levels of autophagy-related proteins, including Parkin, PINK1, p62, ATG12, and LC3, were analyzed by western blot, and cell autophagy was visualized by immunofluorescence.
  
  
  
  RLA increased cell viability and decreased apoptosis, intracellular ROS, and cytotoxicity, and induced cell autophagy in PD models induced by 6-OHDA and MPTP. RLA also reversed the decreased dopamine and increased α-synuclein expression induced by 6-OHDA and MPTP. The mitochondrial regulatory protein PGC-1α was significantly up-regulated by RLA. The expression levels of autophagy-related proteins, including Parkin, PINK1, p62, and ATG12, were down-regulated after RLA treatment, while LC3 expression was up-regulated.
  
  
  
  RLA has a protective effect against cellular damage induced by 6-OHDA and MPTP. The neuroprotective mechanism of RLA may be associated with improvement of mitochondrial function and autophagy. Therefore, RLA may serve as a promising potential adjuvant for PD treatment.
authors.affiliation: Department of Neurology, The Fourth Affiliate Clinical Hospital, Harbin Medical University, Harbin 150001 China. Electronic address: hongzhao113@hotmail.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Neurology, The Fourth Affiliate Clinical Hospital, Harbin Medical University, Harbin 150001 China.
authors.forename: Xingcheng
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Neurology, The Fourth Affiliate Clinical Hospital, Harbin Medical University, Harbin 150001 China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Neurology, The Fourth Affiliate Clinical Hospital, Harbin Medical University, Harbin 150001 China.
authors.forename: Hongxu
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Neurology, The Fourth Affiliate Clinical Hospital, Harbin Medical University, Harbin 150001 China.
authors.forename: Mingwen
authors.initials: M
authors.lastname: Xuan
authors.affiliation: Department of Neurology, The Fourth Affiliate Clinical Hospital, Harbin Medical University, Harbin 150001 China.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Department of Neurology, The Fourth Affiliate Clinical Hospital, Harbin Medical University, Harbin 150001 China.
authors.forename: Hongcai
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Neurology, The Fourth Affiliate Clinical Hospital, Harbin Medical University, Harbin 150001 China.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D010300:Parkinson Disease / Q000188:drug therapy / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D008063:Thioctic Acid / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D008063:Thioctic Acid
keywords: Neuroprotection; Neurotoxin; Parkinson’s disease; R form α-lipoic acid; SH-SY5Y cells