Astaxanthin suppresses endoplasmic reticulum stress and protects against neuron damage in Parkinson's disease by regulating miR-7/SNCA axis.

Autor: Shen DF; Department of Neurology, The Fourth Clinical College of Harbin Medical University, Harbin, 150001, PR China., Qi HP; Department of Neurology, The Fourth Clinical College of Harbin Medical University, Harbin, 150001, PR China., Ma C; Department of Neurology, The Fourth Clinical College of Harbin Medical University, Harbin, 150001, PR China., Chang MX; Department of Neurology, The Fourth Clinical College of Harbin Medical University, Harbin, 150001, PR China., Zhang WN; Department of Neurology, The Fourth Clinical College of Harbin Medical University, Harbin, 150001, PR China., Song RR; Department of Neurology, The Fourth Clinical College of Harbin Medical University, Harbin, 150001, PR China. Electronic address: rongrongsong99@hotmail.com.
Jazyk: angličtina
Zdroj: Neuroscience research [Neurosci Res] 2021 Apr; Vol. 165, pp. 51-60. Date of Electronic Publication: 2020 Apr 22.
DOI: 10.1016/j.neures.2020.04.003
Abstrakt: Parkinson's disease (PD) is a common neurodegenerative disorder that featured by the loss of dopaminergic neurons. Astaxanthin (AST), an important antioxidant, is demonstrated to be a neuroprotective agent for PD. However, the underlying mechanisms of AST in PD remain largely unclear. In this study, we found that AST treatment significantly not only abolished the cell viability inhibition and apoptosis promotion induced by 1-methyl-4-phenylpyridinium (MPP+) in SH-SY5Y cells via inhibiting endoplasmic reticulum (ER) stress, but also reversed the MPP+ caused dysregulation of miR-7 and SNCA expression. MiR-7 knockdown and SNCA overexpression were achieved by treating SH-SY5Y cells with miR-7 inhibitor and pcDNA3.1-SNCA plasmids, respectively. MiR-7 could bind to and negatively regulate SNCA in SH-SY5Y cells. Treated SH-SY5Y cells with miR-7 inhibitor or pcDNA3.1-SNCA abrogated the protective effects of AST on MPP+ induced cytotoxicity. Knockdown of miR-7 aggravated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced neuron injury in vivo suggested by athletic performance, histopathological morphology, expression of tyrosine hydroxylase (TH) and TUNEL positvie cells, however, AST treatment could reverse these effects of miR-7 knockdown. Collectively, AST suppressed ER stress and protected against PD-caused neuron damage by targeting miR-7/SNCA axis, implying that AST might be a potential effective therapeutic agent for PD.
(Copyright © 2020 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.)
Databáze: MEDLINE
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