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

Molecular Medicine Reports
Mei LiuChunyu Wang

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 d...Continue Reading

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Citations

Feb 11, 2020·Frontiers in Neuroscience·Luis D Bernal-CondeMagdalena Guerra-Crespo
Jul 25, 2019·Cells·José Ángel Martínez-MenárguezEmma Martínez-Alonso
Jul 30, 2020·International Journal of Molecular Sciences·Tiffany J Rios-FullerRobert J Schneider
Dec 3, 2020·Frontiers in Cell and Developmental Biology·Yu-Mi JeonHyung-Jun Kim
Jun 3, 2021·International Journal of Molecular Sciences·Panagiota Mavroeidi, Maria Xilouri
Jun 26, 2021·Frontiers in Aging Neuroscience·Haigang RenGuanghui Wang
Jun 15, 2021·Frontiers in Cell and Developmental Biology·Bipul RayMeena Kishore Sakharkar

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Datasets Mentioned

BETA
GM130

Methods Mentioned

BETA
flow
ELISA
enzyme-linked immunosorbent assay
Transfection
flow cytometry

Software Mentioned

Image J
GraphPad Prism
ImageJ
SPSS

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