Overexpression of -synuclein in an astrocyte cell line promotes autophagy inhibition and apoptosis

Overexpression of -synuclein in an astrocyte cell line promotes autophagy inhibition and apoptosis

Author Erustes, Adolfo Garcia Autor UNIFESP Google Scholar
Stefani, Fernanda Yakel Autor UNIFESP Google Scholar
Terashima, Juliana Yoshie Autor UNIFESP Google Scholar
Stilhano, Roberta Sessa Autor UNIFESP Google Scholar
Monteforte, Priscila Totarelli Autor UNIFESP Google Scholar
da Silva Pereira, Gustavo Jose Autor UNIFESP Google Scholar
Han, Sang Won Autor UNIFESP Google Scholar
Calgarotto, Andrana Karla Google Scholar
Hsu, Yi-Te Google Scholar
Ureshino, Rodrigo Portes Autor UNIFESP Google Scholar
Bincoletto, Claudia Autor UNIFESP Google Scholar
Smaili, Soraya Soubhi Autor UNIFESP Google Scholar
Abstract 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.
Keywords Parkinson disease
xmlui.dri2xhtml.METS-1.0.item-coverage Hoboken
Language English
Sponsor Fundacao do Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
Date 2018
Published in Journal Of Neuroscience Research. Hoboken, v. 96, n. 1, p. 160-171, 2018.
ISSN 0360-4012 (Sherpa/Romeo, impact factor)
Publisher Wiley
Extent 160-171
Origin http://dx.doi.org/10.1002/jnr.24092
Access rights Closed access
Type Article
Web of Science ID WOS:000425811000016
URI https://repositorio.unifesp.br/handle/11600/53861

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