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

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dc.citation.issue1
dc.citation.volume96
dc.contributor.authorErustes, Adolfo Garcia [UNIFESP]
dc.contributor.authorStefani, Fernanda Yakel [UNIFESP]
dc.contributor.authorTerashima, Juliana Yoshie [UNIFESP]
dc.contributor.authorStilhano, Roberta Sessa [UNIFESP]
dc.contributor.authorMonteforte, Priscila Totarelli [UNIFESP]
dc.contributor.authorda Silva Pereira, Gustavo Jose [UNIFESP]
dc.contributor.authorHan, Sang Won [UNIFESP]
dc.contributor.authorCalgarotto, Andrana Karla
dc.contributor.authorHsu, Yi-Te
dc.contributor.authorUreshino, Rodrigo Portes [UNIFESP]
dc.contributor.authorBincoletto, Claudia [UNIFESP]
dc.contributor.authorSmaili, Soraya Soubhi [UNIFESP]
dc.coverageHoboken
dc.date.accessioned2020-07-02T18:52:04Z
dc.date.available2020-07-02T18:52:04Z
dc.date.issued2018
dc.description.abstractα‐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.en
dc.description.affiliationFed Univ Sao Paulo UNIFESP, Dept Pharmacol, EPM, Sao Paulo, Brazil
dc.description.affiliationFed Univ Sao Paulo UNIFESP, Dept Biophys, Cellular & Mol Gene Therapy Ctr, EPM, Sao Paulo, Brazil
dc.description.affiliationState Univ Campinas UNICAMP, Dept Pharmacol, Campinas, SP, Brazil
dc.description.affiliationMed Univ South Carolina, Dept Biochem & Mol Biol, Charleston, SC USA
dc.description.affiliationUnifespFed Univ Sao Paulo UNIFESP, Dept Pharmacol, EPM, Sao Paulo, Brazil
dc.description.affiliationUnifespFed Univ Sao Paulo UNIFESP, Dept Biophys, Cellular & Mol Gene Therapy Ctr, EPM, Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundacao do Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
dc.format.extent160-171
dc.identifierhttp://dx.doi.org/10.1002/jnr.24092
dc.identifier.citationJournal Of Neuroscience Research. Hoboken, v. 96, n. 1, p. 160-171, 2018.
dc.identifier.doi10.1002/jnr.24092
dc.identifier.fileWOS000425811000016.pdf
dc.identifier.issn0360-4012
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/53861
dc.identifier.wosWOS:000425811000016
dc.language.isoeng
dc.publisherWiley
dc.relation.ispartofJournal Of Neuroscience Research
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectParkinson diseaseen
dc.subject-synucleinen
dc.subjectA30Pen
dc.subjectA53Ten
dc.subjectparkinen
dc.subjectautophagyen
dc.titleOverexpression of -synuclein in an astrocyte cell line promotes autophagy inhibition and apoptosisen
dc.typeinfo:eu-repo/semantics/article
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