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α‑synuclein induces apoptosis of astrocytes by causing dysfunction of the endoplasmic reticulum‑Golgi compartment

  • Authors:
    • Mei Liu
    • Lixia Qin
    • Lili Wang
    • Jieqiong Tan
    • Hainan Zhang
    • Jianguang Tang
    • Xiangmin Shen
    • Liming Tan
    • Chunyu Wang
  • View Affiliations / Copyright

    Affiliations: Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China, State Key Laboratory of Medical Genetics, Changsha, Hunan 410013, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 322-332
    |
    Published online on: May 9, 2018
       https://doi.org/10.3892/mmr.2018.9002
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Abstract

Although previous work has demonstrated that the overexpression of wild‑type or mutant α‑synuclein (α‑syn) can induce cell death via a number of different mechanisms, including oxidative stress, dysfunction of the ubiquitin‑proteasome degradation system, mitochondrial damage and endoplasmic reticulum (ER) stress, research interest has primarily focused on neurons. However, there is accumulating evidence that suggests that astrocytes may be involved in the earliest changes, as well as the progression of Parkinson's disease (PD), though the role of α‑syn in astrocytes has not been widely studied. In the present study, it was revealed that the mutant α‑syn (A53T and A30P) in astrocytes triggered ER stress via the protein kinase RNA‑like ER kinase/eukaryotic translation initiation factor 2α signaling pathway. Astrocyte apoptosis was induced through a CCAAT‑enhancer‑binding protein homologous protein‑mediated pathway. In addition, Golgi fragmentation was observed in the process. On the other hand, it was also demonstrated, in a primary neuronal‑astroglial co‑culture system, that the overexpression of α‑syn significantly decreased the levels of glia‑derived neurotrophic factor (GDNF) and partly inhibited neurite outgrowth. Although direct evidence is currently lacking, it was proposed that dysfunction of the ER‑Golgi compartment in astrocytes overexpressing α‑syn may lead to a decline of GDNF levels, which in turn would suppress neurite outgrowth. Taken together, the results of the present study offer further insights into the pathogenesis of PD from the perspective of astrocytes, which may provide novel strategies for the diagnosis and treatment of PD in the future.
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Copy and paste a formatted citation
Spandidos Publications style
Liu M, Qin L, Wang L, Tan J, Zhang H, Tang J, Shen X, Tan L and Wang C: α‑synuclein induces apoptosis of astrocytes by causing dysfunction of the endoplasmic reticulum‑Golgi compartment. Mol Med Rep 18: 322-332, 2018.
APA
Liu, M., Qin, L., Wang, L., Tan, J., Zhang, H., Tang, J. ... Wang, C. (2018). α‑synuclein induces apoptosis of astrocytes by causing dysfunction of the endoplasmic reticulum‑Golgi compartment. Molecular Medicine Reports, 18, 322-332. https://doi.org/10.3892/mmr.2018.9002
MLA
Liu, M., Qin, L., Wang, L., Tan, J., Zhang, H., Tang, J., Shen, X., Tan, L., Wang, C."α‑synuclein induces apoptosis of astrocytes by causing dysfunction of the endoplasmic reticulum‑Golgi compartment". Molecular Medicine Reports 18.1 (2018): 322-332.
Chicago
Liu, M., Qin, L., Wang, L., Tan, J., Zhang, H., Tang, J., Shen, X., Tan, L., Wang, C."α‑synuclein induces apoptosis of astrocytes by causing dysfunction of the endoplasmic reticulum‑Golgi compartment". Molecular Medicine Reports 18, no. 1 (2018): 322-332. https://doi.org/10.3892/mmr.2018.9002
Copy and paste a formatted citation
x
Spandidos Publications style
Liu M, Qin L, Wang L, Tan J, Zhang H, Tang J, Shen X, Tan L and Wang C: α‑synuclein induces apoptosis of astrocytes by causing dysfunction of the endoplasmic reticulum‑Golgi compartment. Mol Med Rep 18: 322-332, 2018.
APA
Liu, M., Qin, L., Wang, L., Tan, J., Zhang, H., Tang, J. ... Wang, C. (2018). α‑synuclein induces apoptosis of astrocytes by causing dysfunction of the endoplasmic reticulum‑Golgi compartment. Molecular Medicine Reports, 18, 322-332. https://doi.org/10.3892/mmr.2018.9002
MLA
Liu, M., Qin, L., Wang, L., Tan, J., Zhang, H., Tang, J., Shen, X., Tan, L., Wang, C."α‑synuclein induces apoptosis of astrocytes by causing dysfunction of the endoplasmic reticulum‑Golgi compartment". Molecular Medicine Reports 18.1 (2018): 322-332.
Chicago
Liu, M., Qin, L., Wang, L., Tan, J., Zhang, H., Tang, J., Shen, X., Tan, L., Wang, C."α‑synuclein induces apoptosis of astrocytes by causing dysfunction of the endoplasmic reticulum‑Golgi compartment". Molecular Medicine Reports 18, no. 1 (2018): 322-332. https://doi.org/10.3892/mmr.2018.9002
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