Genetic and Chemical Activation of TFEB Mediates Clearance of Aggregated α-Synuclein

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dc.citation.firstpagee0120819
dc.citation.issueNumber3
dc.citation.journalTitlePLoS ONE
dc.citation.volumeNumber10
dc.contributor.authorKilpatrick, Kiri
dc.contributor.authorZeng, Yimeng
dc.contributor.authorHancock, Tommy
dc.contributor.authorSegatori, Laura
dc.date.accessioned2016-03-28T20:49:40Z
dc.date.available2016-03-28T20:49:40Z
dc.date.issued2015
dc.description.abstractAggregation of α-synuclein (α-syn) is associated with the development of a number of neurodegenerative diseases, including Parkinson’s disease (PD). The formation of α-syn aggregates results from aberrant accumulation of misfolded α-syn and insufficient or impaired activity of the two main intracellular protein degradation systems, namely the ubiquitin-proteasome system and the autophagy-lysosomal pathway. In this study, we investigated the role of transcription factor EB (TFEB), a master regulator of the autophagy-lysosomal pathway, in preventing the accumulation of α-syn aggregates in human neuroglioma cells. We found that TFEB overexpression reduces the accumulation of aggregated α-syn by inducing autophagic clearance of α-syn. Furthermore, we showed that pharmacological activation of TFEB using 2-hydroxypropyl-β-cyclodextrin promotes autophagic clearance of aggregated α-syn. In summary, our findings demonstrate that TFEB modulates autophagic clearance of α-syn and suggest that pharmacological activation of TFEB is a promising strategy to enhance the degradation of α-syn aggregates.
dc.identifier.citationKilpatrick, Kiri, Zeng, Yimeng, Hancock, Tommy, et al.. "Genetic and Chemical Activation of TFEB Mediates Clearance of Aggregated α-Synuclein." <i>PLoS ONE,</i> 10, no. 3 (2015) Public Library of Science: e0120819. http://dx.doi.org/10.1371/journal.pone.0120819.
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pone.0120819
dc.identifier.urihttps://hdl.handle.net/1911/88660
dc.language.isoeng
dc.publisherPublic Library of Science
dc.rightsThis is an open access article distributed under the terms of the�Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.titleGenetic and Chemical Activation of TFEB Mediates Clearance of Aggregated α-Synuclein
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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