Open Access

Overexpression of miR‑185 inhibits autophagy and apoptosis of dopaminergic neurons by regulating the AMPK/mTOR signaling pathway in Parkinson's disease

  • Authors:
    • Zhi Wen
    • Jie Zhang
    • Peng Tang
    • Ning Tu
    • Ke Wang
    • Guangyao Wu
  • View Affiliations

  • Published online on: October 26, 2017     https://doi.org/10.3892/mmr.2017.7897
  • Pages:131-137
  • Copyright: © Wen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Parkinson's disease (PD) is an age‑associated neurodegenerative disorder characterized by the death of dopaminergic neurons in the substantia nigra pars compacta. Activation of 5'‑adenosine monophosphate‑activated protein kinase (AMPK) has been suggested to be associated with PD pathogenesis. The aim of the present study was to investigate the effects of the aberrant expression of microRNA‑185 (miR‑185) in PD. A 1‑methyl‑4‑phenyl‑1,2,3,6‑tetrahydropyridine (MPTP)‑induced in vitro model of PD was generated using the human SH‑SY5Y dopaminergic neuroblastoma cell line, in order to examine the potential molecular mechanisms underlying the roles of miR‑185 in PD. miR‑185 expression was assessed in MPTP-treated SH‑SY5Y cells using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). In addition, MPTP‑treated SH‑SY5Y cells were transfected with a miR‑185 mimic or scramble miRNA, and flow cytometry was used to evaluate the level of cellular apoptosis. The expression of autophagy markers, including Beclin 1, microtubule-associated protein light chain 3 (LC3) I and LC3II, as well as key molecules involved in the AMPK/mechanistic target of rapamycin (mTOR) signaling pathway, such as phosphorylated (p)‑AMPK and p‑mTOR, was examined using RT‑qPCR and western blot analyses. In addition, SH‑SY5Y cells were treated with the AMPK inhibitor, Compound C, and its effects on cellular apoptosis were assessed. The results demonstrated that miR‑185 was significantly downregulated in SH‑SY5Y cells treated with MPTP at concentrations of >100 µM when compared with untreated controls. Following transfection with a miR‑185 mimic, miR‑185 expression in SH‑SY5Y cells was significantly increased when compared with blank control cells. Notably, miR‑185 overexpression was revealed to significantly reduce the MPTP‑induced increase in cellular apoptosis. In addition, the expression levels of Beclin 1, LC3I/II, p‑AMPK and p‑mTOR were significantly upregulated in MPTP‑treated SH‑SY5Y cells; whereas miR‑185 overexpression significantly downregulated the expression of these factors. Furthermore, miR‑185 overexpression significantly suppressed apoptosis of SH‑SY5Y cells treated with MPTP plus Compound C when compared with the Compound C group. In conclusion, the results of the present study suggest that overexpression of miR‑185 may inhibit autophagy and apoptosis of dopaminergic cells in PD potentially via regulation of the AMPK/mTOR signaling pathway. Therefore, AMPK/mTOR‑mediated autophagy and apoptotic signaling pathways may be potential novel therapeutic targets for the development of alternative strategies for the treatment of patients with PD.

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January 2018
Volume 17 Issue 1

Print ISSN: 1791-2997
Online ISSN:1791-3004

2016 Impact Factor: 1.692
Ranked #19/128 Medicine Research and Experimental
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APA
Wen, Z., Zhang, J., Tang, P., Tu, N., Wang, K., & Wu, G. (2018). Overexpression of miR‑185 inhibits autophagy and apoptosis of dopaminergic neurons by regulating the AMPK/mTOR signaling pathway in Parkinson's disease. Molecular Medicine Reports, 17, 131-137. https://doi.org/10.3892/mmr.2017.7897
MLA
Wen, Z., Zhang, J., Tang, P., Tu, N., Wang, K., Wu, G."Overexpression of miR‑185 inhibits autophagy and apoptosis of dopaminergic neurons by regulating the AMPK/mTOR signaling pathway in Parkinson's disease". Molecular Medicine Reports 17.1 (2018): 131-137.
Chicago
Wen, Z., Zhang, J., Tang, P., Tu, N., Wang, K., Wu, G."Overexpression of miR‑185 inhibits autophagy and apoptosis of dopaminergic neurons by regulating the AMPK/mTOR signaling pathway in Parkinson's disease". Molecular Medicine Reports 17, no. 1 (2018): 131-137. https://doi.org/10.3892/mmr.2017.7897