Open Access

α-synuclein promotes progression of Parkinson's disease by upregulating autophagy signaling pathway to activate NLRP3 inflammasome

  • Authors:
    • Xiaohong Wang
    • Jinghong Chi
    • Di Huang
    • Li Ding
    • Xiaojing Zhao
    • Lai Jiang
    • Yang Yu
    • Feng Gao
  • View Affiliations

  • Published online on: December 5, 2019     https://doi.org/10.3892/etm.2019.8297
  • Pages: 931-938
  • Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Mechanism by which α-synuclein affects the progression of Parkinson's disease through Pyrin Domain Containing Protein 3 (NLRP3) was explored. Peripheral blood plasma of 40 Parkinson's disease patients and 40 normal healthy people attending the department of neurology of the Third Affiliated Hospital of Qiqihar Medical University were collected from March 2018 to January 2019. The expression levels of oligomers, phosphorylated α-synuclein, interleukin-1β (IL-1β), interleukin-6 (IL-6) and transforming growth factor-α (TGF-α) in plasma were detected by ELISA. Astrocytes in mouse brain tissues were extracted by primary culture method, the cells were divided into drug group and the drug + inhibitor group. After adding 0, 5, 10 and 20 µg oligomerized α-synuclein or 5 mM autophagy inhibitor 3-Methyladenine (3-MA), the expression level of NLRP3, caspase-1, IL-1β and Atg5 proteins in the cells was detected. The expression level of IL-1β in peripheral blood of PD patients was significantly increased (0.604±0.136 µmol/l vs. 1.876±0.327 µmol/l, P=0.002), while there was no significant difference between IL-6 and TGF-α. Both oligomers (0.171±0.045 µmol/l vs. 0.676±0.084 µmol/l, P<0.0001) and phosphorylated α-synuclein (0.128±0.041 µmol/l vs. 0.849±0.108 µmol/l, P<0.0001) in peripheral blood of PD patients were significantly elevated. The expression levels of NLRP3, caspase-1 and IL-1β in mouse astrocytes all increased with the increase of the concentration of oligomerized α-synuclein, and Atg5 protein expression also increased gradually with the concentration, and reached the highest level when the concentration was 10 µg/ml. The expression levels of NLRP3, caspase-1 and IL-1β were inhibited after the addition of autophagy inhibitor 3-MA. α-synuclein mediates the activation of NLRP3 inflammasome in PD patients by up­regulating Atg5 protein expression.
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February-2020
Volume 19 Issue 2

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Wang X, Chi J, Huang D, Ding L, Zhao X, Jiang L, Yu Y and Gao F: α-synuclein promotes progression of Parkinson's disease by upregulating autophagy signaling pathway to activate NLRP3 inflammasome. Exp Ther Med 19: 931-938, 2020
APA
Wang, X., Chi, J., Huang, D., Ding, L., Zhao, X., Jiang, L. ... Gao, F. (2020). α-synuclein promotes progression of Parkinson's disease by upregulating autophagy signaling pathway to activate NLRP3 inflammasome. Experimental and Therapeutic Medicine, 19, 931-938. https://doi.org/10.3892/etm.2019.8297
MLA
Wang, X., Chi, J., Huang, D., Ding, L., Zhao, X., Jiang, L., Yu, Y., Gao, F."α-synuclein promotes progression of Parkinson's disease by upregulating autophagy signaling pathway to activate NLRP3 inflammasome". Experimental and Therapeutic Medicine 19.2 (2020): 931-938.
Chicago
Wang, X., Chi, J., Huang, D., Ding, L., Zhao, X., Jiang, L., Yu, Y., Gao, F."α-synuclein promotes progression of Parkinson's disease by upregulating autophagy signaling pathway to activate NLRP3 inflammasome". Experimental and Therapeutic Medicine 19, no. 2 (2020): 931-938. https://doi.org/10.3892/etm.2019.8297