Show simple item record

dc.contributor.authorCho, Jin A.en_US
dc.contributor.authorZhang, Xuanen_US
dc.contributor.authorMiller, Gregory M.en_US
dc.contributor.authorLencer, Wayne I.en_US
dc.contributor.authorNery, Flavia C.en_US
dc.date.accessioned2014-12-02T21:27:02Z
dc.date.issued2014en_US
dc.identifier.citationCho, Jin A., Xuan Zhang, Gregory M. Miller, Wayne I. Lencer, and Flavia C. Nery. 2014. “4-Phenylbutyrate Attenuates the ER Stress Response and Cyclic AMP Accumulation in DYT1 Dystonia Cell Models.” PLoS ONE 9 (11): e110086. doi:10.1371/journal.pone.0110086. http://dx.doi.org/10.1371/journal.pone.0110086.en
dc.identifier.issn1932-6203en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:13454622
dc.description.abstractDystonia is a neurological disorder in which sustained muscle contractions induce twisting and repetitive movements or abnormal posturing. DYT1 early-onset primary dystonia is the most common form of hereditary dystonia and is caused by deletion of a glutamic acid residue (302/303) near the carboxyl-terminus of encoded torsinA. TorsinA is localized primarily within the contiguous lumen of the endoplasmic reticulum (ER) and nuclear envelope (NE), and is hypothesized to function as a molecular chaperone and an important regulator of the ER stress-signaling pathway, but how the mutation in torsinA causes disease remains unclear. Multiple lines of evidence suggest that the clinical symptoms of dystonia result from abnormalities in dopamine (DA) signaling, and possibly involving its down-stream effector adenylate cyclase that produces the second messenger cyclic adenosine-3′, 5′-monophosphate (cAMP). Here we find that mutation in torsinA induces ER stress, and inhibits the cyclic adenosine-3′, 5′-monophosphate (cAMP) response to the adenylate cyclase agonist forskolin. Both defective mechanins are corrected by the small molecule 4-phenylbutyrate (4-PBA) that alleviates ER stress. Our results link torsinA, the ER-stress-response, and cAMP-dependent signaling, and suggest 4-PBA could also be used in dystonia treatment. Other pharmacological agents known to modulate the cAMP cascade, and ER stress may also be therapeutic in dystonia patients and can be tested in the models described here, thus supplementing current efforts centered on the dopamine pathway.en
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.relation.isversionofdoi:10.1371/journal.pone.0110086en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4224384/pdf/en
dash.licenseLAAen_US
dc.subjectBiology and Life Sciencesen
dc.subjectCell Biologyen
dc.subjectMolecular Cell Biologyen
dc.subjectMolecular Biologyen
dc.subjectNeuroscienceen
dc.subjectBehavioral Neuroscienceen
dc.subjectCellular Neuroscienceen
dc.subjectCognitive Neuroscienceen
dc.subjectCognitive Scienceen
dc.subjectDevelopmental Neuroscienceen
dc.subjectMolecular Neuroscienceen
dc.title4-Phenylbutyrate Attenuates the ER Stress Response and Cyclic AMP Accumulation in DYT1 Dystonia Cell Modelsen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalPLoS ONEen
dash.depositing.authorZhang, Xuanen_US
dc.date.available2014-12-02T21:27:02Z
dc.identifier.doi10.1371/journal.pone.0110086*
dash.contributor.affiliatedNery, Flavia C.
dash.contributor.affiliatedZhang, Xuan
dash.contributor.affiliatedLencer, Wayne


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record