{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:53:49Z","timestamp":1790805229621,"version":"4.1.0"},"reference-count":29,"publisher":"Portland Press Ltd.","issue":"20","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,10,15]]},"abstract":"<jats:p>Glycogen storage disorders (GSDs) are caused by excessive accumulation of glycogen. Some GSDs [adult polyglucosan (PG) body disease (APBD), and Tarui and Lafora diseases] are caused by intracellular accumulation of insoluble inclusions, called PG bodies (PBs), which are chiefly composed of malconstructed glycogen. We developed an APBD patient skin fibroblast cell-based assay for PB identification, where the bodies are identified as amylase-resistant periodic acid\u2013Schiff's-stained structures, and quantified. We screened the DIVERSet CL 10\u2009084 compound library using this assay in high-throughput format and discovered 11 dose-dependent and 8 non-dose-dependent PB-reducing hits. Approximately 70% of the hits appear to act through reducing glycogen synthase (GS) activity, which can elongate glycogen chains and presumably promote PB generation. Some of these GS inhibiting hits were also computationally predicted to be similar to drugs interacting with the GS activator protein phosphatase 1. Our work paves the way to discovering medications for the treatment of PB-involving GSD, which are extremely severe or fatal disorders.<\/jats:p>","DOI":"10.1042\/bcj20170469","type":"journal-article","created":{"date-parts":[[2017,8,22]],"date-time":"2017-08-22T00:20:14Z","timestamp":1503361214000},"page":"3403-3420","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["A novel image-based high-throughput screening assay discovers therapeutic candidates for adult polyglucosan body disease"],"prefix":"10.1042","volume":"474","author":[{"given":"Leonardo J.","family":"Solmesky","sequence":"first","affiliation":[{"name":"Cell Screening Facility for Personalized Medicine, Department of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Netaly","family":"Khazanov","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Bar Ilan University, Ramat Gan, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanoch","family":"Senderowitz","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Bar Ilan University, Ramat Gan, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peixiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Program in Genetics and Genome Biology, The Hospital for Sick Children, University of Toronto, Toronto, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berge A.","family":"Minassian","sequence":"additional","affiliation":[{"name":"Program in Genetics and Genome Biology, The Hospital for Sick Children, University of Toronto, Toronto, Canada"},{"name":"Department of Pediatrics, University of Texas Southwestern, Dallas, TX, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor M.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Structural Genomics Consortium, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wyatt W.","family":"Yue","sequence":"additional","affiliation":[{"name":"Structural Genomics Consortium, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Lossos","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hadassah Medical Center, Hebrew University of Jerusalem Israel, Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Weil","sequence":"additional","affiliation":[{"name":"Cell Screening Facility for Personalized Medicine, Department of Cell Research and Immunology, The Sagol School of Neurosciences, The George S. 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