{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T14:52:28Z","timestamp":1788187948849,"version":"build-2803163510"},"reference-count":79,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,7,2]],"date-time":"2020-07-02T00:00:00Z","timestamp":1593648000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100002019","name":"Children's Fund for Glycogen Storage Disease Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002019","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Glycogen storage disease type Ia (GSD\u2010Ia) is an inherited metabolic disease caused by a deficiency in glucose\u20106\u2010phosphatase\u2010\u03b1 (G6Pase\u2010\u03b1 or G6PC) which plays a critical role in blood glucose homeostasis by catalyzing the hydrolysis of glucose\u20106\u2010phosphate (G6P) to glucose and phosphate in the terminal step of glycogenolysis and gluconeogenesis. Patients with GSD\u2010Ia manifest life\u2010threatening fasting hypoglycemia along with the excessive accumulation of hepatic glycogen and triglycerides which results in hepatomegaly and a risk of long\u2010term complications such as hepatocellular adenoma and carcinoma (HCA\/HCC). The etiology of HCA\/HCC development in GSD\u2010Ia, however, is unknown. Recent studies have shown that the livers in model animals of GSD\u2010Ia display impairment of autophagy, a cellular recycling process which is critical for energy metabolism and cellular homeostasis. However, molecular mechanisms of autophagy impairment and its involvement in pathogenesis in GSD\u2010Ia are still under investigation. Here, we summarize the latest advances for signaling pathways implicated in hepatic autophagy impairment and the roles of autophagy in hepatic tumorigenesis in GSD\u2010Ia. In addition, recent evidence has illustrated that autophagy plays an important role in hepatic metabolism and liver\u2010directed gene therapy mediated by recombinant adeno\u2010associated virus (rAAV). Therefore, we highlight the possible role of hepatic autophagy in metabolic control and rAAV\u2010mediated gene therapy for GSD\u2010Ia. In this review, we also provide potential therapeutic strategies for GSD\u2010Ia on the basis of molecular mechanisms underlying hepatic autophagy impairment in GSD\u2010Ia.<\/jats:p>","DOI":"10.1002\/jimd.12267","type":"journal-article","created":{"date-parts":[[2020,5,31]],"date-time":"2020-05-31T12:59:22Z","timestamp":1590929962000},"page":"118-128","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Emerging roles of autophagy in hepatic tumorigenesis and therapeutic strategies in glycogen storage disease type Ia: A review"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8756-8824","authenticated-orcid":false,"given":"Jun\u2010Ho","family":"Cho","sequence":"first","affiliation":[{"name":"Glycogen Storage Disease Program, Department of Pediatrics University of Connecticut School of Medicine  Farmington Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Weinstein","sequence":"additional","affiliation":[{"name":"Glycogen Storage Disease Program, Department of Pediatrics University of Connecticut School of Medicine  Farmington Connecticut USA"},{"name":"Glycogen Storage Disease Program Connecticut Children's Medical Center  Hartford Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Mok","family":"Lee","sequence":"additional","affiliation":[{"name":"Glycogen Storage Disease Program, Department of Pediatrics University of Connecticut School of Medicine  Farmington Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,7,2]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.15698\/cst2019.03.179"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2010.189"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-018-0192-1"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2018.07.017"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2019.11.061"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.10.026"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.08.026"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.10.008"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006819"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddaa007"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2152"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3716"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.11.006"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2012.32"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.19653"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2008.03.003"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1196371"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.24399"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.6.682"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02583"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2009.02.006"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2008.11.008"},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M608310200"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3262"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00270.2015"},{"key":"e_1_2_14_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2014.01.021"},{"key":"e_1_2_14_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep44408"},{"key":"e_1_2_14_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.03.048"},{"key":"e_1_2_14_30_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201102031"},{"key":"e_1_2_14_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.04.043"},{"key":"e_1_2_14_32_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.2016211"},{"key":"e_1_2_14_33_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.118976"},{"key":"e_1_2_14_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.10.035"},{"key":"e_1_2_14_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.05.023"},{"key":"e_1_2_14_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02072092"},{"key":"e_1_2_14_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2007.04.024"},{"key":"e_1_2_14_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2013.123"},{"key":"e_1_2_14_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2082"},{"key":"e_1_2_14_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-07338-z"},{"key":"e_1_2_14_41_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20140341"},{"key":"e_1_2_14_42_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00005.2014"},{"key":"e_1_2_14_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2016.415"},{"key":"e_1_2_14_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29389"},{"key":"e_1_2_14_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2013.02.003"},{"key":"e_1_2_14_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2012.09.030"},{"key":"e_1_2_14_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2018.03.083"},{"key":"e_1_2_14_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-013-0890-2"},{"key":"e_1_2_14_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp441"},{"key":"e_1_2_14_50_1","first-page":"147","article-title":"Glycogen synthase kinase\u20103: functions in oncogenesis and development","volume":"1114","author":"Plyte SE","year":"1992","journal-title":"Biochim Biophys Acta"},{"key":"e_1_2_14_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2018.04.023"},{"key":"e_1_2_14_52_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/4629495"},{"key":"e_1_2_14_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/8904_2014_344"},{"key":"e_1_2_14_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/pedi.12540"},{"key":"e_1_2_14_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-017-0054-2"},{"key":"e_1_2_14_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2011.02.031"},{"key":"e_1_2_14_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2007.10.134"},{"key":"e_1_2_14_58_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-005-7500-2"},{"key":"e_1_2_14_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2014.35"},{"key":"e_1_2_14_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2018.07.006"},{"key":"e_1_2_14_61_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddy343"},{"key":"e_1_2_14_62_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddz290"},{"key":"e_1_2_14_63_1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2019.0007"},{"key":"e_1_2_14_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.livres.2018.09.004"},{"key":"e_1_2_14_65_1","first-page":"410","article-title":"Direct evidence of sirtuin downregulation in the liver of non\u2010alcoholic fatty liver disease patients","volume":"44","author":"Wu T","year":"2014","journal-title":"Ann Clin Lab Sci"},{"key":"e_1_2_14_66_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200421270"},{"key":"e_1_2_14_67_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2017.6637"},{"key":"e_1_2_14_68_1","doi-asserted-by":"publisher","DOI":"10.4161\/15548627.2014.984271"},{"key":"e_1_2_14_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2013.08.036"},{"key":"e_1_2_14_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2019.02.002"},{"key":"e_1_2_14_71_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2010.64"},{"key":"e_1_2_14_72_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.25717"},{"key":"e_1_2_14_73_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-018-0199-7"},{"key":"e_1_2_14_74_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-018-0223-y"},{"key":"e_1_2_14_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2019.10.016"},{"key":"e_1_2_14_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2017.11.007"},{"key":"e_1_2_14_77_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2010.175"},{"key":"e_1_2_14_78_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29176"},{"key":"e_1_2_14_79_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1549"},{"key":"e_1_2_14_80_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-09-599266"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jimd.12267","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jimd.12267","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jimd.12267","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T06:26:02Z","timestamp":1692253562000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jimd.12267"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,2]]},"references-count":79,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,1]]}},"alternative-id":["10.1002\/jimd.12267"],"URL":"https:\/\/doi.org\/10.1002\/jimd.12267","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,2]]},"assertion":[{"value":"2020-03-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-07-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}