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Overexpression of α‐synuclein in an astrocyte cell line promotes autophagy inhibition and apoptosis
Author(s) -
Erustes Adolfo Garcia,
Stefani Fernanda Yakel,
Terashima Juliana Yoshie,
Stilhano Roberta Sessa,
Monteforte Priscila Totarelli,
da Silva Pereira Gustavo José,
Han Sang Won,
Calgarotto Andrana Karla,
Hsu YiTe,
Ureshino Rodrigo Portes,
Bincoletto Cláudia,
Smaili Soraya Soubhi
Publication year - 2018
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.24092
Subject(s) - autophagy , microbiology and biotechnology , astrocyte , parkin , neuroprotection , apoptosis , rotenone , biology , programmed cell death , cell culture , cytoplasm , neurodegeneration , mitochondrion , parkinson's disease , neuroscience , biochemistry , central nervous system , pathology , disease , medicine , genetics
α‐Synuclein is the major component of neuronal cytoplasmic aggregates called Lewy bodies, the main pathological hallmark of Parkinson disease. Although neurons are the predominant cells expressing α‐synuclein in the brain, recent studies have demonstrated that primary astrocytes in culture also express α‐synuclein and regulate α‐synuclein trafficking. Astrocytes have a neuroprotective role in several detrimental brain conditions; we therefore analyzed the effects of the overexpression of wild‐type α‐synuclein and its A30P and A53T mutants on autophagy and apoptosis. We observed that in immortalized astrocyte cell lines, overexpression of α‐synuclein proteins promotes the decrease of LC3‐II and the increase of p62 protein levels, suggesting the inhibition of autophagy. When these cells were treated with rotenone, there was a loss of mitochondrial membrane potential, especially in cells expressing mutant α‐synuclein. The level of this decrease was related to the toxicity of the mutants because they show a more intense and sustained effect. The decrease in autophagy and the mitochondrial changes in conjunction with parkin expression levels may sensitize astrocytes to apoptosis.