{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T13:11:49Z","timestamp":1768482709840,"version":"3.49.0"},"reference-count":37,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,10,9]],"date-time":"2020-10-09T00:00:00Z","timestamp":1602201600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01NS097197"],"award-info":[{"award-number":["P01NS097197"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DK27221"],"award-info":[{"award-number":["R01DK27221"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Adult polyglucosan body disease (APBD) is an adult\u2010onset neurological variant of glycogen storage disease type IV. APBD is caused by recessive mutations in the glycogen branching enzyme gene, and the consequent accumulation of poorly branched glycogen aggregates called polyglucosan bodies in the nervous system. There are presently no treatments for APBD. Here, we test whether downregulation of glycogen synthesis is therapeutic in a mouse model of the disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We characterized the effects of knocking out two pro\u2010glycogenic proteins in an APBD mouse model. APBD mice were crossed with mice deficient in glycogen synthase (GYS1), or mice deficient in protein phosphatase 1 regulatory subunit 3C (PPP1R3C), a protein involved in the activation of GYS1. Phenotypic and histological parameters were analyzed and glycogen was quantified.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>APBD mice deficient in GYS1 or PPP1R3C demonstrated improvements in life span, morphology, and behavioral assays of neuromuscular function. Histological analysis revealed a reduction in polyglucosan body accumulation and of astro\u2010 and micro\u2010gliosis in the brains of GYS1\u2010 and PPP1R3C\u2010deficient APBD mice. Brain glycogen quantification confirmed the reduction in abnormal glycogen accumulation. Analysis of skeletal muscle, heart, and liver found that GYS1 deficiency reduced polyglucosan body accumulation in all three tissues and PPP1R3C knockout reduced skeletal muscle polyglucosan bodies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>GYS1 and PPP1R3C are effective therapeutic targets in the APBD mouse model. These findings represent a critical step toward the development of a treatment for APBD and potentially other glycogen storage disease type IV patients.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51211","type":"journal-article","created":{"date-parts":[[2020,10,9]],"date-time":"2020-10-09T10:18:28Z","timestamp":1602238708000},"page":"2186-2198","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["GYS1 or PPP1R3C deficiency rescues murine adult polyglucosan body disease"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1144-0821","authenticated-orcid":false,"given":"Erin E.","family":"Chown","sequence":"first","affiliation":[{"name":"Genetics and Genome Biology Program The Hospital for Sick Children Peter Gilgan Centre for Research and Learning Toronto Ontario Canada"},{"name":"Institute of Medical Science University of Toronto Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peixiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Genetics and Genome Biology Program The Hospital for Sick Children Peter Gilgan Centre for Research and Learning Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaochu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Genetics and Genome Biology Program The Hospital for Sick Children Peter Gilgan Centre for Research and Learning Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin J.","family":"Crowder","sequence":"additional","affiliation":[{"name":"Indiana University School of Medicine\u2010Muncie Ball State University Muncie Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jordan W.","family":"Strober","sequence":"additional","affiliation":[{"name":"Indiana University School of Medicine\u2010Muncie Ball State University Muncie Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitchell A.","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Genetics and Genome Biology Program The Hospital for Sick Children Peter Gilgan Centre for Research and Learning Toronto Ontario Canada"},{"name":"Glycation and Diabetes Mater Research Institute\u2010University of Queensland Translational Research Institute Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunlin","family":"Xue","sequence":"additional","affiliation":[{"name":"Genetics and Genome Biology Program The Hospital for Sick Children Peter Gilgan Centre for Research and Learning Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cody S.","family":"Bennett","sequence":"additional","affiliation":[{"name":"Indiana University School of Medicine\u2010Muncie Ball State University Muncie Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ami M.","family":"Perri","sequence":"additional","affiliation":[{"name":"Genetics and Genome Biology Program The Hospital for Sick Children Peter Gilgan Centre for Research and Learning Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5686-0315","authenticated-orcid":false,"given":"Bret M.","family":"Evers","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Texas Southwestern Dallas Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter J.","family":"Roach","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna A.","family":"Depaoli\u2010Roach","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H. 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