{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T18:18:49Z","timestamp":1788286729426,"version":"build-2803163510"},"reference-count":61,"publisher":"The Company of Biologists","issue":"5-6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,4,28]]},"abstract":"<jats:title>SUMMARY<\/jats:title><jats:p>Movement disorders represent a significant societal burden for which therapeutic options are limited and focused on treating disease symptomality. Early-onset torsion dystonia (EOTD) is one such disorder characterized by sustained and involuntary muscle contractions that frequently cause repetitive movements or abnormal postures. Transmitted in an autosomal dominant manner with reduced penetrance, EOTD is caused in most cases by the deletion of a glutamic acid (\u0394E) in the DYT1 (also known as TOR1A) gene product, torsinA. Although some patients respond well to anticholingerics, therapy is primarily limited to either neurosurgery or chemodenervation. As mutant torsinA (\u0394E) expression results in decreased torsinA function, therapeutic strategies directed toward enhancement of wild-type (WT) torsinA activity in patients who are heterozygous for mutant DYT1 may restore normal cellular functionality. Here, we report results from the first-ever screen for candidate small molecule therapeutics for EOTD, using multiple activity-based readouts for torsinA function in Caenorhabditis elegans, subsequent validation in human DYT1 patient fibroblasts, and behavioral rescue in a mouse model of DYT1 dystonia. We exploited the nematode to rapidly discern chemical effectors of torsinA and identified two classes of antibiotics, quinolones and aminopenicillins, which enhance WT torsinA activity in two separate in vivo assays. Representative molecules were assayed in EOTD patient fibroblasts for improvements in torsinA-dependent secretory function, which was improved significantly by ampicillin. Furthermore, a behavioral defect associated with an EOTD mouse knock-in model was also rescued following administration of ampicillin. These combined data indicate that specific small molecules that enhance torsinA activity represent a promising new approach toward therapeutic development for EOTD, and potentially for other diseases involving the processing of mutant proteins.<\/jats:p>","DOI":"10.1242\/dmm.003715","type":"journal-article","created":{"date-parts":[[2010,3,11]],"date-time":"2010-03-11T21:53:39Z","timestamp":1268344419000},"page":"386-396","source":"Crossref","is-referenced-by-count":51,"title":["Chemical enhancement of torsinA function in cell and animal models of torsion dystonia"],"prefix":"10.1242","volume":"3","author":[{"given":"Songsong","family":"Cao","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, The University of Alabama, Tuscaloosa, AL 35487, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey W.","family":"Hewett","sequence":"additional","affiliation":[{"name":"Departments of Neurology and Radiology, Massachusetts General Hospital, MA 02114, USA"},{"name":"Program in Neuroscience, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumiaki","family":"Yokoi","sequence":"additional","affiliation":[{"name":"Department of Neurology and Center for Neurodegeneration and Experimental Therapeutics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Neurology and Center for Neurodegeneration and Experimental Therapeutics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amber Clark","family":"Buckley","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, The University of Alabama, Tuscaloosa, AL 35487, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander J.","family":"Burdette","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, The University of Alabama, Tuscaloosa, AL 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settings","volume":"23","author":"Lipinski","year":"1997","journal-title":"Adv Drug Deliv Rev"},{"key":"2021042500171257200_b39-0030386","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1042\/bj20030258","article-title":"Characterization of human torsinA and its dystonia-associated mutant form","volume":"374","author":"Liu","year":"2003","journal-title":"Biochem J"},{"key":"2021042500171257200_b40-0030386","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.brainres.2006.08.067","article-title":"Genetic interactions among cortical malformation genes that influence susceptibility to convulsions in C. elegans","volume":"1120","author":"Locke","year":"2006","journal-title":"Brain Res"},{"key":"2021042500171257200_b41-0030386","doi-asserted-by":"crossref","first-page":"34412","DOI":"10.1074\/jbc.M704134200","article-title":"Caenorhabditis elegans glutamate transporters influence synaptic function and behavior at sites distant from the synapse","volume":"282","author":"Mano","year":"2007","journal-title":"J Biol Chem"},{"key":"2021042500171257200_b42-0030386","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1046\/j.1471-4159.2002.01190.x","article-title":"torsinA and heat shock proteins act as molecular chaperones: suppression of alpha-synuclein aggregation","volume":"83","author":"McLean","year":"2002","journal-title":"J Neurochem"},{"key":"2021042500171257200_b43-0030386","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1002\/ana.20225","article-title":"Brainstem pathology in DYT1 primary torsion dystonia","volume":"56","author":"McNaught","year":"2004","journal-title":"Ann Neurol"},{"key":"2021042500171257200_b44-0030386","doi-asserted-by":"crossref","first-page":"6934","DOI":"10.1093\/emboj\/18.24.6934","article-title":"Identification of thermolabile Escherichia coli proteins: prevention and reversion of aggregation by DnaK and ClpB","volume":"18","author":"Mogk","year":"1999","journal-title":"EMBO J"},{"key":"2021042500171257200_b45-0030386","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1002\/neu.20313","article-title":"Down-regulation of torp4a, encoding the Drosophila homologue of torsinA, results in increased neuronal degeneration","volume":"66","author":"Muraro","year":"2006","journal-title":"J Neurobiol"},{"key":"2021042500171257200_b46-0030386","doi-asserted-by":"crossref","first-page":"7612","DOI":"10.1073\/pnas.0308760101","article-title":"TorsinA in the nuclear envelope","volume":"101","author":"Naismith","year":"2004","journal-title":"Proc Natl Acad Sci USA"},{"key":"2021042500171257200_b47-0030386","doi-asserted-by":"crossref","first-page":"3476","DOI":"10.1242\/jcs.029454","article-title":"TorsinA binds the KASH domain of nesprins and participates in linkage between nuclear envelope and cytoskeleton","volume":"121","author":"Nery","year":"2008","journal-title":"J Cell 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