{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:24:18Z","timestamp":1790767458681,"version":"4.1.0"},"reference-count":129,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T00:00:00Z","timestamp":1715558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Autophagy is an evolutionarily conserved lysosome-dependent degradation of cytoplasmic constituents. The system operates as a critical cellular pro-survival mechanism in response to nutrient deprivation and a variety of stress conditions. On top of that, autophagy is involved in maintaining cellular homeostasis through selective elimination of worn-out or damaged proteins and organelles. The autophagic pathway is largely responsible for the delivery of cytosolic glycogen to the lysosome where it is degraded to glucose via acid \u03b1-glucosidase. Although the physiological role of lysosomal glycogenolysis is not fully understood, its significance is highlighted by the manifestations of Pompe disease, which is caused by a deficiency of this lysosomal enzyme. Pompe disease is a severe lysosomal glycogen storage disorder that affects skeletal and cardiac muscles most. In this review, we discuss the basics of autophagy and describe its involvement in the pathogenesis of muscle damage in Pompe disease. Finally, we outline how autophagic pathology in the diseased muscles can be used as a tool to fast track the efficacy of therapeutic interventions.<\/jats:p>","DOI":"10.3390\/biom14050573","type":"journal-article","created":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T08:59:37Z","timestamp":1715677177000},"page":"573","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Failure of Autophagy in Pompe Disease"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7027-9938","authenticated-orcid":false,"given":"Hung","family":"Do","sequence":"first","affiliation":[{"name":"M6P Therapeutics, 20 S. Sarah Street, St. Louis, MO 63108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5450-5184","authenticated-orcid":false,"given":"Naresh K.","family":"Meena","sequence":"additional","affiliation":[{"name":"M6P Therapeutics, 20 S. Sarah Street, St. Louis, MO 63108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Raben","sequence":"additional","affiliation":[{"name":"M6P Therapeutics, 20 S. Sarah Street, St. Louis, MO 63108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"740","DOI":"10.4161\/auto.6398","article-title":"Autophagy revisited: A conversation with Christian de Duve","volume":"4","author":"Klionsky","year":"2008","journal-title":"Autophagy"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/cr.2013.169","article-title":"Historical landmarks of autophagy research","volume":"24","author":"Ohsumi","year":"2013","journal-title":"Cell Res."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Gudmundsson, S.R., Kallio, K.A., Vihinen, H., Jokitalo, E., Ktistakis, N., and Eskelinen, E.-L. (2022). Morphology of Phagophore Precursors by Correlative Light-Electron Microscopy. Cells, 11.","DOI":"10.3390\/cells11193080"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"21883","DOI":"10.1074\/jbc.273.34.21883","article-title":"Isolation and characterization of rat liver amphisomes. Evidence for fusion of autophagosomes with both early and late endosomes","volume":"273","author":"Berg","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/cr.2013.168","article-title":"The machinery of macroautophagy","volume":"24","author":"Feng","year":"2013","journal-title":"Cell Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.15252\/embj.201796697","article-title":"Molecular definitions of autophagy and related processes","volume":"36","author":"Galluzzi","year":"2017","journal-title":"EMBO J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1038\/nature09076","article-title":"Termination of autophagy and reformation of lysosomes regulated by mTOR","volume":"465","author":"Yu","year":"2010","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1038\/s41580-018-0001-6","article-title":"The coming of age of chaperone-mediated autophagy","volume":"19","author":"Kaushik","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Oku, M., and Sakai, Y. (2018). Three Distinct Types of Microautophagy Based on Membrane Dynamics and Molecular Machineries. BioEssays, 40.","DOI":"10.1002\/bies.201800008"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/s41580-022-00529-z","article-title":"The emerging mechanisms and functions of microautophagy","volume":"24","author":"Wang","year":"2022","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"719","DOI":"10.4161\/auto.19469","article-title":"Autophagy in lysosomal storage disorders","volume":"8","author":"Lieberman","year":"2012","journal-title":"Autophagy"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1042\/EBC20170055","article-title":"Dysregulation of autophagy as a common mechanism in lysosomal storage diseases","volume":"61","author":"Seranova","year":"2017","journal-title":"Essays Biochem."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Myerowitz, R., Puertollano, R., and Raben, N. (2020). Impaired autophagy: The collateral damage of lysosomal storage disorders. EBioMedicine, 63.","DOI":"10.1016\/j.ebiom.2020.103166"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5720","DOI":"10.1093\/emboj\/19.21.5720","article-title":"LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing","volume":"19","author":"Kabeya","year":"2000","journal-title":"EMBO J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/978-1-59745-157-4_4","article-title":"LC3 and Autophagy","volume":"445","author":"Tanida","year":"2008","journal-title":"Methods Mol Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.jmb.2019.05.010","article-title":"History of the Selective Autophagy Research: How Did It Begin and Where Does It Stand Today?","volume":"432","author":"Kirkin","year":"2020","journal-title":"J. Mol. Biol."},{"key":"ref_17","first-page":"233","article-title":"Cargo recognition and degradation by selective autophagy","volume":"20","author":"Gatica","year":"2018","journal-title":"Nature"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1083\/jcb.200507002","article-title":"p62\/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on hunting-tin-induced cell death","volume":"171","author":"Lamark","year":"2005","journal-title":"J. Cell Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"24131","DOI":"10.1074\/jbc.M702824200","article-title":"p62\/SQSTM1 binds directly to Atg8\/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy","volume":"282","author":"Pankiv","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/s41580-022-00542-2","article-title":"The mechanisms and roles of selective autophagy in mammals","volume":"24","author":"Vargas","year":"2022","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"546","DOI":"10.4161\/auto.4591","article-title":"Deconstructing pompe disease by analyzing single muscle fibers: \u201cTo see a world in a grain of sand\u2026\u201d","volume":"3","author":"Raben","year":"2007","journal-title":"Autophagy"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"112037","DOI":"10.1016\/j.celrep.2023.112037","article-title":"The selective autophagy adaptor p62\/SQSTM1 forms phase condensates regulated by HSP27 that facilitate the clearance of damaged lysosomes via lysophagy","volume":"42","author":"Gallagher","year":"2023","journal-title":"Cell Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1126\/science.1174447","article-title":"A gene network regulating lysosomal biogenesis and function","volume":"325","author":"Sardiello","year":"2009","journal-title":"Science"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"ra9","DOI":"10.1126\/scisignal.2004754","article-title":"The Nutrient-Responsive Transcription Factor TFE3 Promotes Autophagy, Lysosomal Biogenesis, and Clearance of Cellular Debris","volume":"7","author":"Martina","year":"2014","journal-title":"Sci. Signal."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1126\/science.1204592","article-title":"TFEB links autophagy to lysosomal biogenesis","volume":"332","author":"Settembre","year":"2011","journal-title":"Science"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.devcel.2011.07.016","article-title":"Transcriptional activation of lysosomal exocytosis promotes cellular clearance","volume":"21","author":"Medina","year":"2011","journal-title":"Dev. Cell"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Settembre, C., and Ballabio, A. (2014). Lysosomal Adaptation: How the Lysosome Responds to External Cues. Cold Spring Harb. Perspect. Biol., 6.","DOI":"10.1101\/cshperspect.a016907"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"903","DOI":"10.4161\/auto.19653","article-title":"MTORC1 functions as a transcriptional regulator of autophagy by preventing nuclear transport of TFEB","volume":"8","author":"Martina","year":"2012","journal-title":"Autophagy"},{"key":"ref_29","first-page":"ra42","article-title":"The transcription factor TFEB links mTORC1 signaling to transcriptional control of lysosome homeostasis","volume":"5","author":"Petit","year":"2012","journal-title":"Sci. Signal."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1038\/ncb3114","article-title":"Lysosomal calcium signalling regulates autophagy through calcineurin and TFEB","volume":"17","author":"Medina","year":"2015","journal-title":"Nat. Cell Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1083\/jcb.201607005","article-title":"The lysosome as a command-and-control center for cellular metabolism","volume":"214","author":"Lim","year":"2016","journal-title":"J. Cell Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e98804","DOI":"10.15252\/embj.201798804","article-title":"The complex relationship between TFEB transcription factor phosphorylation and subcellular localization","volume":"37","author":"Puertollano","year":"2018","journal-title":"EMBO J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"25464","DOI":"10.1074\/jbc.M703663200","article-title":"siRNA screening of the kinome identifies ULK1 as a multidomain modulator of autophagy","volume":"282","author":"Chan","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1038\/ncb2152","article-title":"AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1","volume":"13","author":"Kim","year":"2011","journal-title":"Nat. Cell Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1146\/annurev-pharmtox-010611-134537","article-title":"AMPK and mTOR in cellular energy homeostasis and drug targets","volume":"52","author":"Inoki","year":"2012","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1042\/BJ20080281","article-title":"The TSC1\u2013TSC2 complex: A molecular switchboard controlling cell growth","volume":"412","author":"Huang","year":"2008","journal-title":"Biochem. J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/j.cell.2013.11.049","article-title":"Spatial control of the TSC complex integrates insulin and nutrient regulation of mTORC1 at the lysosome","volume":"156","author":"Menon","year":"2014","journal-title":"Cell"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"10662","DOI":"10.1038\/ncomms10662","article-title":"Lysosomal recruitment of TSC2 is a universal response to cellular stress","volume":"7","author":"Demetriades","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Inpanathan, S., and Botelho, R.J. (2019). The Lysosome Signaling Platform: Adapting With the Times. Front. Cell Dev. Biol., 7.","DOI":"10.3389\/fcell.2019.00113"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1016\/j.cell.2017.02.004","article-title":"mTOR Signaling in Growth, Metabolism, and Disease","volume":"168","author":"Saxton","year":"2017","journal-title":"Cell"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/nrm3565","article-title":"Signals from the lysosome: A control centre for cellular clearance and energy metabolism","volume":"14","author":"Settembre","year":"2013","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1146\/annurev-cellbio-111315-125407","article-title":"TFEB and TFE3: Linking Lysosomes to Cellular Adaptation to Stress","volume":"32","author":"Raben","year":"2016","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.tibs.2020.09.004","article-title":"How Lysosomes Sense, Integrate, and Cope with Stress","volume":"46","author":"Saftig","year":"2021","journal-title":"Trends Biochem. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.ymgme.2016.12.004","article-title":"The emerging phenotype of late-onset Pompe disease: A systematic literature review","volume":"120","author":"Chan","year":"2017","journal-title":"Mol. Genet. Metab."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1111\/dmcn.13740","article-title":"Classic infantile Pompe patients approaching adulthood: A cohort study on consequences for the brain","volume":"60","author":"Ebbink","year":"2018","journal-title":"Dev. Med. Child Neurol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1007\/s13311-018-0655-y","article-title":"Pompe Disease: From Basic Science to Therapy","volume":"15","author":"Kohler","year":"2018","journal-title":"Neurotherapeutics"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.jpeds.2005.11.033","article-title":"A retrospective, multinational, multicenter study on the natural history of infantile-onset Pompe disease","volume":"148","author":"Kishnani","year":"2006","journal-title":"J. Pediatr."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"284","DOI":"10.21037\/atm.2019.07.24","article-title":"Multisystem late onset Pompe disease (LOPD): An update on clinical aspects","volume":"7","author":"Toscano","year":"2019","journal-title":"Ann. Transl. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1002\/ajmg.a.35662","article-title":"How to describe the clinical spectrum in Pompe disease","volume":"161","author":"Reuser","year":"2013","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2146","DOI":"10.1002\/humu.23878","article-title":"GAA variants and phenotypes among 1079 patients with Pompe disease: Data from the Pompe Registry","volume":"40","author":"Reuser","year":"2019","journal-title":"Hum. Mutat."},{"key":"ref_51","unstructured":"Reuser, A.J., and Schoser, B. (2021). Pompe Disease, UNI-MED Verlag AG. [3rd ed.]."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1542\/peds.2016-0280C","article-title":"Newborn Screening for Pompe Disease","volume":"140","author":"Bodamer","year":"2017","journal-title":"Pediatrics"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Tang, H., Feuchtbaum, L., Sciortino, S., Matteson, J., Mathur, D., Bishop, T., and Olney, R.S. (2020). The First Year Experience of Newborn Screening for Pompe Disease in California. Int. J. Neonatal Screen., 6.","DOI":"10.3390\/ijns6010009"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1007\/s11940-022-00736-1","article-title":"Pompe Disease: A Clinical, Diagnostic, and Therapeutic Overview","volume":"24","author":"Stevens","year":"2022","journal-title":"Curr. Treat. Options Neurol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/S0092-8674(88)80026-6","article-title":"The mannose 6-phosphate receptor and the biogenesis of lysosomes","volume":"52","author":"Griffiths","year":"1988","journal-title":"Cell"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"12115","DOI":"10.1016\/S0021-9258(18)63825-6","article-title":"Mannose 6-phosphate receptors and lysosomal enzyme targeting","volume":"264","author":"Dahms","year":"1989","journal-title":"J. Biol. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1038\/nrm1050","article-title":"Mannose 6-phosphate receptors: New twists in the tale","volume":"4","author":"Ghosh","year":"2003","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/nrm2745","article-title":"Lysosome biogenesis and lysosomal membrane proteins: Trafficking meets function","volume":"10","author":"Saftig","year":"2009","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2223","DOI":"10.1016\/S0021-9258(18)53985-5","article-title":"Structural and functional changes of lysosomal acid alpha-glucosidase during intracellular transport and maturation","volume":"268","author":"Wisselaar","year":"1993","journal-title":"J. Biol. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"6780","DOI":"10.1074\/jbc.M404008200","article-title":"Lysosomal acid alpha-glucosidase consists of four different peptides processed from a single chain pre-cursor","volume":"280","author":"Moreland","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"19086","DOI":"10.1074\/jbc.273.30.19086","article-title":"Targeted disruption of the acid \u03b1-glucosidase gene in mice causes an illness with critical features of both infantile and adult human glycogen storage disease type II","volume":"273","author":"Raben","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.ymgme.2003.08.022","article-title":"Enzyme replacement therapy in the mouse model of Pompe disease","volume":"80","author":"Raben","year":"2003","journal-title":"Mol. Genet. Metab."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1093\/hmg\/7.1.53","article-title":"Generalized glycogen storage and cardiomegaly in a knockout mouse model of Pompe disease","volume":"7","author":"Bijvoet","year":"1998","journal-title":"Hum. Mol. Genet."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1002\/mus.20270","article-title":"Age-related decline in muscle strength and power output in acid 1-4 alpha-glucosidase knockout mice","volume":"31","author":"Hesselink","year":"2005","journal-title":"Muscle Nerve"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1093\/brain\/93.3.599","article-title":"Acid maltase deficiency in adults: Studies in four cases of a syndrome which may mimic muscular dystrophy or other myopathies","volume":"93","author":"Engel","year":"1970","journal-title":"Brain"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.ymthe.2004.09.017","article-title":"Replacing acid alpha-glucosidase in Pompe disease: Recombinant and transgenic enzymes are equipotent, but neither completely clears glycogen from type II muscle fibers","volume":"11","author":"Raben","year":"2005","journal-title":"Mol. Ther."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1002\/ana.20807","article-title":"Dysfunction of endocytic and autophagic pathways in a lysosomal storage disease","volume":"59","author":"Fukuda","year":"2006","journal-title":"Ann. Neurol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/2051-5960-2-2","article-title":"The value of muscle biopsies in Pompe disease: Identifying lipofuscin inclusions in juvenile- and adult-onset patients","volume":"2","author":"Feeney","year":"2014","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.jpeds.2006.02.035","article-title":"Chinese hamster ovary cell-derived recombinant human acid \u03b1-glucosidase in infantile-onset Pompe disease","volume":"149","author":"Kishnani","year":"2006","journal-title":"J. Pediatr."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1212\/01.wnl.0000407271.54424.a2","article-title":"Recombinant human acid \u03b1-glucosidase: Major clinical benefits in infantile-onset Pompe disease","volume":"77","author":"Kishnani","year":"2011","journal-title":"Neurology"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1203\/PDR.0b013e3181b24e94","article-title":"Early treatment with alglucosidase alpha prolongs long-term survival of infants with pompe disease","volume":"66","author":"Kishnani","year":"2009","journal-title":"Pediatr. Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1186\/1750-1172-8-90","article-title":"Skeletal muscle pathology of infantile Pompe disease during long-term enzyme replacement therapy","volume":"8","author":"Prater","year":"2013","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"283","DOI":"10.21037\/atm.2019.04.70","article-title":"Long-term outcome and unmet needs in infantile-onset Pompe disease","volume":"7","author":"Hahn","year":"2019","journal-title":"Ann. Transl. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2482","DOI":"10.1007\/s00415-021-10409-9","article-title":"STIG study: Real-world data of long-term outcomes of adults with Pompe disease under enzyme re-placement therapy with alglucosidase alfa","volume":"268","author":"Gutschmidt","year":"2021","journal-title":"J. Neurol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1007\/s11910-003-0040-y","article-title":"Autophagic vacuolar myopathies","volume":"3","author":"Nishino","year":"2003","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1111\/bpa.12864","article-title":"Differential diagnosis of vacuolar myopathies in the NGS era","volume":"30","author":"Mair","year":"2020","journal-title":"Brain Pathol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.omtm.2020.05.026","article-title":"Enzyme Replacement Therapy Can Reverse Pathogenic Cascade in Pompe Disease","volume":"18","author":"Meena","year":"2020","journal-title":"Mol. Ther.-Methods Clin. Dev."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/j.ymthe.2006.08.009","article-title":"Autophagy and mistargeting of therapeutic enzyme in skeletal muscle in pompe disease","volume":"14","author":"Fukuda","year":"2006","journal-title":"Mol. Ther."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"318","DOI":"10.4161\/auto.2984","article-title":"Autophagy and lysosomes in pompe disease","volume":"2","author":"Fukuda","year":"2006","journal-title":"Autophagy"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1002\/emmm.201202176","article-title":"Transcription factor EB (TFEB) is a new therapeutic target for Pompe disease","volume":"5","author":"Spampanato","year":"2013","journal-title":"EMBO Mol. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/j.jsb.2008.03.010","article-title":"Detection and imaging of non-contractile inclusions and sarcomeric anomalies in skeletal muscle by second harmonic generation combined with two-photon excited fluorescence","volume":"162","author":"Ralston","year":"2008","journal-title":"J. Struct. Biol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"111","DOI":"10.4161\/auto.5.1.7293","article-title":"When more is less: Excess and deficiency of autophagy coexist in skeletal muscle in Pompe disease","volume":"5","author":"Raben","year":"2009","journal-title":"Autophagy"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"445","DOI":"10.4161\/auto.19496","article-title":"Guidelines for the use and interpretation of assays for monitoring autophagy","volume":"8","author":"Klionsky","year":"2012","journal-title":"Autophagy"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e2565","DOI":"10.1038\/cddis.2016.475","article-title":"Autophagy dysregulation in Danon disease","volume":"8","author":"Nascimbeni","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"353","DOI":"10.15252\/emmm.201606547","article-title":"Modulation of mTOR signaling as a strategy for the treatment of Pompe disease","volume":"9","author":"Lim","year":"2017","journal-title":"EMBO Mol. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1016\/j.ymthe.2018.04.025","article-title":"Therapeutic Benefit of Autophagy Modulation in Pompe Disease","volume":"26","author":"Lim","year":"2018","journal-title":"Mol. Ther."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1083\/jcb.52.1.41","article-title":"Autophagic degradation of glycogen in skeletal muscles of the newborn rat","volume":"52","author":"Schiaffino","year":"1972","journal-title":"J. Cell Biol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1002\/jemt.20046","article-title":"Glycogen autophagy","volume":"64","author":"Kotoulas","year":"2004","journal-title":"Microsc. Res. Tech."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.prp.2006.04.001","article-title":"Glycogen autophagy in glucose homeostasis","volume":"202","author":"Kotoulas","year":"2006","journal-title":"Pathol. Res. Pract."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1002\/jemt.20000","article-title":"An electron microscopic and biochemical study of the effects of glucagon on glycogen autophagy in the liver and heart of newborn rats","volume":"63","author":"Kondomerkos","year":"2004","journal-title":"Microsc. Res. Tech."},{"key":"ref_91","first-page":"689","article-title":"Glycogen autophagy in the liver and heart of newborn rats. The effects of glucagon, adrenalin or rapamycin","volume":"20","author":"Kondomerkos","year":"2005","journal-title":"Histol. Histopathol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.4161\/auto.6.8.13378","article-title":"Suppression of autophagy permits successful enzyme replacement therapy in a lysosomal storage disor-der-murine Pompe disease","volume":"6","author":"Raben","year":"2010","journal-title":"Autophagy"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1038\/nature03029","article-title":"The role of autophagy during the early neonatal starvation period","volume":"432","author":"Kuma","year":"2004","journal-title":"Nature"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1083\/jcb.200412022","article-title":"Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice","volume":"169","author":"Komatsu","year":"2005","journal-title":"J. Cell Biol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1080\/15548627.2017.1343770","article-title":"Autophagy-monitoring and autophagy-deficient mice","volume":"13","author":"Kuma","year":"2017","journal-title":"Autophagy"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1042\/BJ20111416","article-title":"Glycogen and its metabolism: Some new developments and old themes","volume":"441","author":"Roach","year":"2012","journal-title":"Biochem. J."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1002\/path.6255","article-title":"Defect in degradation of glycogenin-exposed residual glycogen in lysosomes is the fundamental pathomechanism of Pompe disease","volume":"263","author":"Zhang","year":"2024","journal-title":"J. Pathol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.bbrc.2011.08.106","article-title":"Starch-binding domain-containing protein 1 (Stbd1) and glycogen metabolism: Identification of the Atg8 family interacting motif (AIM) in Stbd1 required for interaction with GABARAPL1","volume":"413","author":"Jiang","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1080\/15548627.2021.1969633","article-title":"Regulation and role of glycophagy in skeletal muscle energy metabolism","volume":"18","author":"Heden","year":"2021","journal-title":"Autophagy"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"34960","DOI":"10.1074\/jbc.M110.150839","article-title":"Starch binding domain-containing protein 1\/genethonin 1 is a novel participant in glycogen metabolism","volume":"285","author":"Jiang","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.ymgme.2013.05.004","article-title":"Stbd1 is highly elevated in skeletal muscle of Pompe disease mice but suppression of its expression does not affect lysosomal glycogen accumulation","volume":"109","author":"Yi","year":"2013","journal-title":"Mol. Genet. Metab."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"16479","DOI":"10.1074\/jbc.C116.741397","article-title":"Starch Binding Domain-containing Protein 1 Plays a Dominant Role in Glycogen Transport to Lysosomes in Liver","volume":"291","author":"Sun","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/nature09204","article-title":"Network organization of the human autophagy system","volume":"466","author":"Behrends","year":"2010","journal-title":"Nature"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Zirin, J., Nieuwenhuis, J., Samsonova, A., Tao, R., and Perrimon, N. (2015). Regulators of Autophagosome Formation in Drosophila Muscles. PLOS Genet., 11.","DOI":"10.1371\/journal.pgen.1005006"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Koutsifeli, P., Varma, U., Daniels, L.J., Annandale, M., Li, X., Neale, J.P.H., Hayes, S., Weeks, K.L., James, S., and Delbridge, L.M.D. (2022). Glycogen-autophagy: Molecular machinery and cellular mechanisms of glycophagy. J. Biol. Chem., 298.","DOI":"10.1016\/j.jbc.2022.102093"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Zirin, J., Nieuwenhuis, J., and Perrimon, N. (2013). Role of autophagy in glycogen breakdown and its relevance to chloroquine myopathy. PLOS Biol., 11.","DOI":"10.1371\/journal.pbio.1001708"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1002\/jimd.12560","article-title":"Lysosomal glycogen accumulation in Pompe disease results in disturbed cytoplasmic glycogen me-tabolism","volume":"46","author":"Harlaar","year":"2023","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"G\u00f3mez-Cebri\u00e1n, N., Gras-Colomer, E., Andr\u00e9s, J.L.P., Pineda-Lucena, A., and Puchades-Carrasco, L. (2023). Omics-Based Approaches for the Characterization of Pompe Disease Metabolic Phenotypes. Biology, 12.","DOI":"10.3390\/biology12091159"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"S\u00e1nchez-Porras, V., Guevara-Morales, J.M., and Echeverri-Pe\u00f1a, O.Y. (2023). From Acid Alpha-Glucosidase Deficiency to Autophagy: Understanding the Bases of POMPE Disease. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241512481"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"eadf1691","DOI":"10.1126\/scitranslmed.adf1691","article-title":"Small-molecule inhibition of glycogen synthase 1 for the treatment of Pompe disease and other glycogen storage disorders","volume":"16","author":"Ullman","year":"2024","journal-title":"Sci. Transl. Med."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1016\/j.tem.2023.07.008","article-title":"Lysosomal glucose sensing and glycophagy in metabolism","volume":"34","author":"Mancini","year":"2023","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1042\/bst0180367","article-title":"Lysosomal enzyme targeting","volume":"18","author":"Kornfeld","year":"1990","journal-title":"Biochem. Soc. Trans."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"291","DOI":"10.21037\/atm.2019.04.15","article-title":"Challenges in treating Pompe disease: An industry perspective","volume":"7","author":"Do","year":"2019","journal-title":"Ann. Transl. Med."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1016\/S1474-4422(21)00241-6","article-title":"Safety and efficacy of avalglucosidase alfa versus alglucosidase alfa in patients with late-onset Pompe disease (COMET): A phase 3, randomised, multicentre trial","volume":"20","author":"Kishnani","year":"2021","journal-title":"Lancet Neurol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1038\/mt.2009.37","article-title":"Glycoengineered acid \u03b1-glucosidase with improved efficacy at correcting the metabolic aberrations and motor function deficits in a mouse model of pompe disease","volume":"17","author":"Zhu","year":"2009","journal-title":"Mol. Ther."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/S1474-4422(21)00358-6","article-title":"New therapies for Pompe disease: Are we closer to a cure?","volume":"20","author":"Puertollano","year":"2021","journal-title":"Lancet Neurol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"e536","DOI":"10.1212\/WNL.0000000000200746","article-title":"Long-term Safety and Efficacy of Avalglucosidase Alfa in Patients With Late-Onset Pompe Disease","volume":"99","author":"Dimachkie","year":"2022","journal-title":"Neurology"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1212\/WNL.0000000000200821","article-title":"Greater Efficacy of Avalglucosidase vs Alglucosidase Alfa in Adult Pompe Disease? The Jury Is Still Out","volume":"99","author":"Argov","year":"2022","journal-title":"Neurology"},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Selvan, N., Mehta, N., Venkateswaran, S., Brignol, N., Graziano, M., Sheikh, M.O., McAnany, Y., Hung, F., Madrid, M., and Krampetz, R. (2021). Endolysosomal N-glycan processing is critical to attain the most active form of the enzyme acid alpha-glucosidase. J. Biol. Chem., 296.","DOI":"10.1016\/j.jbc.2021.100769"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/S1474-4422(21)00331-8","article-title":"Safety and efficacy of cipaglucosidase alfa plus miglustat versus alglucosidase alfa plus placebo in late-onset Pompe disease (PROPEL): An international, randomised, double-blind, parallel-group, phase 3 trial","volume":"20","author":"Schoser","year":"2021","journal-title":"Lancet Neurol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"2810","DOI":"10.1007\/s00415-024-12236-0","article-title":"104-week efficacy and safety of cipaglucosidase alfa plus miglustat in adults with late-onset Pompe disease: A phase III open-label extension study (ATB200-07)","volume":"271","author":"Schoser","year":"2024","journal-title":"J. Neurol."},{"key":"ref_122","first-page":"e125358","article-title":"Improved efficacy of a next-generation ERT in murine Pompe disease","volume":"4","author":"Xu","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.jmb.2019.08.010","article-title":"Repair or Lysophagy: Dealing with Damaged Lysosomes","volume":"432","author":"Papadopoulos","year":"2020","journal-title":"J. Mol. Biol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1529\/biophysj.105.071555","article-title":"Characterization of the myosin-based source for second-harmonic generation from muscle sarcomeres","volume":"90","author":"Plotnikov","year":"2006","journal-title":"Biophys. J."},{"key":"ref_125","first-page":"e170199","article-title":"AAV-mediated delivery of secreted acid \u03b1-glucosidase with enhanced uptake corrects neuromuscular pathology in Pompe mice","volume":"8","author":"Meena","year":"2023","journal-title":"J. Clin. Investig."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.devcel.2019.10.025","article-title":"Galectin-3 Coordinates a Cellular System for Lysosomal Repair and Removal","volume":"52","author":"Jia","year":"2020","journal-title":"Dev. Cell"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1091\/mbc.e03-09-0704","article-title":"In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a flu-orescent autophagosome marker","volume":"15","author":"Mizushima","year":"2004","journal-title":"Mol. Biol. Cell"},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Vaghela, R., Arkudas, A., Horch, R.E., and Hessenauer, M. (2021). Actually Seeing What Is Going on\u2014Intravital Microscopy in Tissue Engineering. Front. Bioeng. Biotechnol., 9.","DOI":"10.3389\/fbioe.2021.627462"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"e1561","DOI":"10.1002\/ctm2.1561","article-title":"Intravital imaging of muscle damage and response to therapy in a model of Pompe disease","volume":"14","author":"Meena","year":"2024","journal-title":"Clin. Transl. Med."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/14\/5\/573\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:41:21Z","timestamp":1760107281000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/14\/5\/573"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,13]]},"references-count":129,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["biom14050573"],"URL":"https:\/\/doi.org\/10.3390\/biom14050573","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,13]]}}}