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

Simple item page
dc.citation.firstpagee0120819en_US
dc.citation.issueNumber3en_US
dc.citation.journalTitlePLoS ONEen_US
dc.citation.volumeNumber10en_US
dc.contributor.authorKilpatrick, Kirien_US
dc.contributor.authorZeng, Yimengen_US
dc.contributor.authorHancock, Tommyen_US
dc.contributor.authorSegatori, Lauraen_US
dc.contributor.orgBioengineeringen_US
dc.contributor.orgBiosciencesen_US
dc.contributor.orgChemical and Biomolecular Engineeringen_US
dc.date.accessioned2016-03-28T20:49:40Zen_US
dc.date.available2016-03-28T20:49:40Zen_US
dc.date.issued2015en_US
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.en_US
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.en_US
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pone.0120819en_US
dc.identifier.urihttps://hdl.handle.net/1911/88660en_US
dc.language.isoengen_US
dc.publisherPublic Library of Scienceen_US
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.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.titleGenetic and Chemical Activation of TFEB Mediates Clearance of Aggregated α-Synucleinen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
journal.pone.0120819.pdf
Size:
11.1 MB
Format:
Adobe Portable Document Format
Description:
Download
Collections
Faculty Publications