{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T05:00:56Z","timestamp":1780635656605,"version":"3.54.1"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T00:00:00Z","timestamp":1699920000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p>Inadequate glycogen branching enzyme 1 (GBE1) activity results in different forms of glycogen storage disease type IV, including adult polyglucosan body disorder (APBD). APBD is clinically characterized by adult-onset development of progressive spasticity, neuropathy, and neurogenic bladder and is histologically characterized by the accumulation of structurally abnormal glycogen (polyglucosan bodies) in multiple cell types. How insufficient GBE1 activity causes the disease phenotype of APBD is poorly understood. We hypothesized that proteomic analysis of tissue from GBE1-deficient individuals would provide insights into GBE1-mediated pathobiology. In this discovery study, we utilized label-free LC\u2013MS\/MS to quantify the proteomes of lymphoblasts from 3 persons with APBD and 15 age- and gender-matched controls, with validation of the findings by targeted MS. There were 531 differentially expressed proteins out of 3,427 detected between APBD subjects vs. controls, including pronounced deficiency of GBE1. Bioinformatic analyses indicated multiple canonical pathways and protein\u2013protein interaction networks to be statistically markedly enriched in APBD subjects, including: RNA processing\/transport\/translation, cell cycle control\/replication, mTOR signaling, protein ubiquitination, unfolded protein and endoplasmic reticulum stress responses, glycolysis and cell death\/apoptosis. Dysregulation of these processes, therefore, are primary or secondary factors in APBD pathobiology in this model system. Our findings further suggest that proteomic analysis of <jats:italic>GBE1<\/jats:italic> mutant lymphoblasts can be leveraged as part of the screening for pharmaceutical agents for the treatment of APBD.<\/jats:p>","DOI":"10.3389\/fneur.2023.1261125","type":"journal-article","created":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T05:13:49Z","timestamp":1700025229000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Proteomic investigations of adult polyglucosan body disease: insights into the pathobiology of a neurodegenerative disorder"],"prefix":"10.3389","volume":"14","author":[{"given":"Joseph R.","family":"Abraham","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick M.","family":"Allen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Barnard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Schlatzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marvin R.","family":"Natowicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,11,14]]},"reference":[{"key":"ref1","article-title":"Glycogen storage diseases","volume-title":"The online metabolic and molecular bases of inherited disease","author":"Chen","year":"2019"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1002\/ana.23598","article-title":"Adult polyglucosan body disease: natural history and key magnetic resonance findings","volume":"72","author":"Mochel","year":"2012","journal-title":"Ann Neurol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1002\/jimd.12325","article-title":"GBE1-related disorders: adult polyglucosan body disease and its neuromuscular phenotypes","volume":"44","author":"Souza","year":"2020","journal-title":"J Inherit Metab Dis"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1001\/jamaneurol.2014.4496","article-title":"Deep intronic GBE1 mutation in manifesting heterozygous patients with adult polyglucosan body disease","volume":"72","author":"Akman","year":"2015","journal-title":"JAMA Neurol"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.mam.2015.08.006","article-title":"Polyglucosan storage myopathies","volume":"46","author":"Hedberg-Oldfors","year":"2015","journal-title":"Mol Asp Med"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"6801","DOI":"10.1093\/hmg\/ddv385","article-title":"A novel mouse model that recapitulates adult-onset glycogenosis type 4","volume":"24","author":"Akman","year":"2015","journal-title":"Hum Molec Genet"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/j.nmd.2014.11.006","article-title":"A novel GBE1 mutation and features of polyglucosan bodies autophagy in adult polyglucosan body disease","volume":"25","author":"Sampaolo","year":"2015","journal-title":"Neuromuscul Disord"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"2343","DOI":"10.1021\/cr3003533","article-title":"Protein analysis by shotgun\/bottom-up proteomics","volume":"113","author":"Zhang","year":"2013","journal-title":"Chem Rev"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1016\/j.neuron.2017.09.025","article-title":"A primer on concepts and applications of proteomics in neuroscience","volume":"96","author":"Hosp","year":"2017","journal-title":"Neuron"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"The ACMG laboratory quality assurance committee. 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