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α-synuclein induces apoptosis of astrocytes by causing dysfunction of the endoplasmic reticulum-Golgi compartment
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 reticulu...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6059687/ https://www.ncbi.nlm.nih.gov/pubmed/29749529 http://dx.doi.org/10.3892/mmr.2018.9002 |
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author | Liu, Mei Qin, Lixia Wang, Lili Tan, Jieqiong Zhang, Hainan Tang, Jianguang Shen, Xiangmin Tan, Liming Wang, Chunyu |
author_facet | Liu, Mei Qin, Lixia Wang, Lili Tan, Jieqiong Zhang, Hainan Tang, Jianguang Shen, Xiangmin Tan, Liming Wang, Chunyu |
author_sort | Liu, Mei |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6059687 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-60596872018-07-26 α-synuclein induces apoptosis of astrocytes by causing dysfunction of the endoplasmic reticulum-Golgi compartment Liu, Mei Qin, Lixia Wang, Lili Tan, Jieqiong Zhang, Hainan Tang, Jianguang Shen, Xiangmin Tan, Liming Wang, Chunyu Mol Med Rep Articles 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. D.A. Spandidos 2018-07 2018-05-09 /pmc/articles/PMC6059687/ /pubmed/29749529 http://dx.doi.org/10.3892/mmr.2018.9002 Text en Copyright: © Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Liu, Mei Qin, Lixia Wang, Lili Tan, Jieqiong Zhang, Hainan Tang, Jianguang Shen, Xiangmin Tan, Liming Wang, Chunyu α-synuclein induces apoptosis of astrocytes by causing dysfunction of the endoplasmic reticulum-Golgi compartment |
title | α-synuclein induces apoptosis of astrocytes by causing dysfunction of the endoplasmic reticulum-Golgi compartment |
title_full | α-synuclein induces apoptosis of astrocytes by causing dysfunction of the endoplasmic reticulum-Golgi compartment |
title_fullStr | α-synuclein induces apoptosis of astrocytes by causing dysfunction of the endoplasmic reticulum-Golgi compartment |
title_full_unstemmed | α-synuclein induces apoptosis of astrocytes by causing dysfunction of the endoplasmic reticulum-Golgi compartment |
title_short | α-synuclein induces apoptosis of astrocytes by causing dysfunction of the endoplasmic reticulum-Golgi compartment |
title_sort | α-synuclein induces apoptosis of astrocytes by causing dysfunction of the endoplasmic reticulum-golgi compartment |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6059687/ https://www.ncbi.nlm.nih.gov/pubmed/29749529 http://dx.doi.org/10.3892/mmr.2018.9002 |
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