{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T03:45:18Z","timestamp":1775274318967,"version":"3.50.1"},"reference-count":63,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T00:00:00Z","timestamp":1765411200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Spanish Ministry of Economy","award":["Rti2018-095784b-100SAF MCI\/AEI\/FEDER, UE"],"award-info":[{"award-number":["Rti2018-095784b-100SAF MCI\/AEI\/FEDER, UE"]}]},{"name":"Tatiana Perez de Guzman el Bueno Foundation"},{"name":"Fondazione Malattie Rare Mauro Baschirotto BIRD Onlus"},{"name":"AEVEL Foundation"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras","award":["ACCI 2020, 23\u2014U744 and\u2014742"],"award-info":[{"award-number":["ACCI 2020, 23\u2014U744 and\u2014742"]}]},{"name":"National Institute of Neurological Disorders and Stroke of the National Institutes of Health","award":["P01NS097197"],"award-info":[{"award-number":["P01NS097197"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Lafora disease is a fatal neurodegenerative disorder caused by loss-of-function mutations in the EPM2A or EPM2B genes, which encode laforin and malin, respectively. These mutations lead to the accumulation of intracellular inclusions of abnormal glycogen, known as Lafora bodies, the hallmark of the disease. Symptoms typically begin in early adolescence with seizures and rapidly progress to cognitive and motor decline, ultimately resulting in dementia and death within a decade of onset. Disruption of Epm2a or Epm2b in mice causes neuronal degeneration and Lafora body accumulation in the brain and other tissues. Epm2a\u2212\/\u2212 and Epm2b\u2212\/\u2212 mice exhibit motor and memory impairments, epileptic activity, and molecular and histological abnormalities. We previously demonstrated that intracerebroventricular delivery of a recombinant adeno-associated virus carrying EPM2A significantly improved pathology in Epm2a\u2212\/\u2212 mice. In this study, we tested recombinant adeno-associated virus-mediated delivery of the human EPM2B gene in Epm2b\u2212\/\u2212 mice. The treatment partially improved neurological, molecular, and histopathological outcomes, although some pathological features persisted. Importantly, our findings reveal differences between EPM2A- and EPM2B-based gene therapies, highlighting the need to better understand their distinct mechanisms. Despite limitations, our study provides new insights into the complexity of targeting EPM2B mutations in Lafora disease.<\/jats:p>","DOI":"10.3390\/ijms262411930","type":"journal-article","created":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T08:39:18Z","timestamp":1765442358000},"page":"11930","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Adeno-Associated Virus-Based Gene Therapy for Lafora Disease in Epm2b-Deficient Mice"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1807-7538","authenticated-orcid":false,"given":"Luis","family":"Zafra-Puerta","sequence":"first","affiliation":[{"name":"Laboratory of Neurology, Instituto de Investigaci\u00f3n Sanitaria-Fundaci\u00f3n Jim\u00e9nez D\u00edaz, Universidad Aut\u00f3noma de Madrid (IIS-FJD, UAM), 28040 Madrid, Spain"},{"name":"Fondazione Malattie Rare Mauro Baschirotto BIRD Onlus, 36023 Longare, VI, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8775-155X","authenticated-orcid":false,"given":"Nerea","family":"Iglesias-Cabeza","sequence":"additional","affiliation":[{"name":"Laboratory of Neurology, Instituto de Investigaci\u00f3n Sanitaria-Fundaci\u00f3n Jim\u00e9nez D\u00edaz, Universidad Aut\u00f3noma de Madrid (IIS-FJD, UAM), 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2399-4103","authenticated-orcid":false,"given":"Pascual","family":"Sanz","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Valencia, CSIC, Jaime Roig 11, 46010 Valencia, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), 46010 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6483-3912","authenticated-orcid":false,"given":"Mar\u00eda Adelaida","family":"Garc\u00eda-Gimeno","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Escuela T\u00e9cnica Superior de Ingenier\u00eda Agron\u00f3mica y del Medio Natural, Universitat Polit\u00e9cnica de Val\u00e8ncia, 46022 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gema","family":"S\u00e1nchez-Mart\u00edn","sequence":"additional","affiliation":[{"name":"Laboratory of Neurology, Instituto de Investigaci\u00f3n Sanitaria-Fundaci\u00f3n Jim\u00e9nez D\u00edaz, Universidad Aut\u00f3noma de Madrid (IIS-FJD, UAM), 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6785-7680","authenticated-orcid":false,"given":"Marina P.","family":"S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Laboratory of Neurology, Instituto de Investigaci\u00f3n Sanitaria-Fundaci\u00f3n Jim\u00e9nez D\u00edaz, Universidad Aut\u00f3noma de Madrid (IIS-FJD, UAM), 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 M.","family":"Serratosa","sequence":"additional","affiliation":[{"name":"Laboratory of Neurology, Instituto de Investigaci\u00f3n Sanitaria-Fundaci\u00f3n Jim\u00e9nez D\u00edaz, Universidad Aut\u00f3noma de Madrid (IIS-FJD, UAM), 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/BF02863929","article-title":"Beitrag zur Histopathologie der Myoklonischen Epilepsie","volume":"6","author":"Lafora","year":"1911","journal-title":"Z. Die Gesamte Neurol. Und Psychiatr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1056\/NEJM198607313150506","article-title":"Progressive myoclonus epilepsies: Specific causes and diagnosis","volume":"315","author":"Berkovic","year":"1986","journal-title":"New Engl. J. Med."},{"key":"ref_3","first-page":"95","article-title":"Progressive Myoclonus Epilepsy with Lafora Bodies","volume":"4","author":"Heycoptenhamm","year":"1963","journal-title":"Clin. Pathol. Features"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1093\/brain\/78.3.325","article-title":"Progressive familial myoclonic epilepsy in three families: Its clinical features and pathological basis","volume":"78","author":"Harriman","year":"1955","journal-title":"Brain A J. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1001\/archneur.1965.00460260062008","article-title":"Lafora\u2019s disease. Distinct clinico-pathologic form of unverricht\u2019s syndrome","volume":"12","author":"Schwarz","year":"1965","journal-title":"Arch. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"66","DOI":"10.33588\/rn.6802.2018100","article-title":"Lafora disease: A review of the literature","volume":"68","author":"Desdentado","year":"2019","journal-title":"Rev. Neurol."},{"key":"ref_7","first-page":"38","article-title":"Lafora disease","volume":"18","author":"Turnbull","year":"2016","journal-title":"Epileptic Disord. Int. Epilepsy J. Videotape"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1093\/hmg\/4.9.1657","article-title":"The gene for progressive myoclonus epilepsy of the Lafora type maps to chromosome 6q","volume":"4","author":"Serratosa","year":"1995","journal-title":"Hum. Mol. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1093\/hmg\/8.2.345","article-title":"A novel protein tyrosine phosphatase gene is mutated in progressive myoclonus epilepsy of the Lafora type (EPM2)","volume":"8","author":"Serratosa","year":"1999","journal-title":"Hum. Mol. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1038\/2470","article-title":"Mutations in a gene encoding a novel protein tyrosine phosphatase cause progressive myoclonus epilepsy","volume":"20","author":"Minassian","year":"1998","journal-title":"Nat. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.1093\/oxfordjournals.hmg.a018916","article-title":"Laforin, defective in the progressive myoclonus epilepsy of Lafora type, is a dual-specificity phosphatase associated with polyribosomes","volume":"9","author":"Ganesh","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1136\/jmg.40.9.671","article-title":"Genetic mapping of a new Lafora progressive myoclonus epilepsy locus (EPM2B) on 6p22","volume":"40","author":"Chan","year":"2003","journal-title":"J. Med. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1038\/ng1238","article-title":"Mutations in NHLRC1 cause progressive myoclonus epilepsy","volume":"35","author":"Chan","year":"2003","journal-title":"Nat. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"8501","DOI":"10.1073\/pnas.0503285102","article-title":"Insights into Lafora disease: Malin is an E3 ubiquitin ligase that ubiquitinates and promotes the degradation of laforin","volume":"102","author":"Gentry","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1038\/nn1998","article-title":"Mechanism suppressing glycogen synthesis in neurons and its demise in progressive myoclonus epilepsy","volume":"10","author":"Vilchez","year":"2007","journal-title":"Nat. Neurosci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"107271","DOI":"10.1016\/j.jbc.2024.107271","article-title":"Impaired malin expression and interaction with partner proteins in Lafora disease","volume":"300","author":"Skurat","year":"2024","journal-title":"J. Biol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1002\/iub.1072","article-title":"Deciphering the role of malin in the lafora progressive myoclonus epilepsy","volume":"64","author":"Sanz","year":"2012","journal-title":"IUBMB Life"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1093\/hmg\/ddm339","article-title":"Regulation of glycogen synthesis by the laforin-malin complex is modulated by the AMP-activated protein kinase pathway","volume":"17","author":"Ros","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"25372","DOI":"10.1074\/jbc.M110.148668","article-title":"Genetic depletion of the malin E3 ubiquitin ligase in mice leads to lafora bodies and the accumulation of insoluble laforin","volume":"285","author":"Tagliabracci","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"7117","DOI":"10.1074\/jbc.R117.803064","article-title":"Lafora disease offers a unique window into neuronal glycogen metabolism","volume":"293","author":"Gentry","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Vernia, S., Rubio, T., Heredia, M., Rodr\u00edguez de C\u00f3rdoba, S., and Sanz, P. (2009). Increased endoplasmic reticulum stress and decreased proteasomal function in lafora disease models lacking the phosphatase laforin. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0005907"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1007\/s12035-014-8747-0","article-title":"Increased oxidative stress and impaired antioxidant response in Lafora disease","volume":"51","author":"Aguado","year":"2015","journal-title":"Mol. Neurobiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.freeradbiomed.2015.01.034","article-title":"Oxidative stress, a new hallmark in the pathophysiology of Lafora progressive myoclonus epilepsy","volume":"88","author":"Aguado","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.1111\/febs.14468","article-title":"Degradation of altered mitochondria by autophagy is impaired in Lafora disease","volume":"285","author":"Lahuerta","year":"2018","journal-title":"FEBS J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3147","DOI":"10.1093\/hmg\/ddu024","article-title":"Glycogen accumulation underlies neurodegeneration and autophagy impairment in Lafora disease","volume":"23","author":"Duran","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/BF01989438","article-title":"\u00dcber das Vorkommen amyloider K\u00f6rperchen im Innern der Ganglienzellen","volume":"205","author":"Lafora","year":"1911","journal-title":"Virchows Arch. F\u00fcr Pathol. Anat. Und Physiol. Und F\u00fcr Klin. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1001\/archneur.1968.00480010033002","article-title":"Studies in myoclonus epilepsy (Lafora body form). I. Isolation and preliminary characterization of Lafora bodies in two cases","volume":"19","author":"Yokoi","year":"1968","journal-title":"Arch. Neurol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1212\/WNL.20.2.160","article-title":"Studies in myoclonus epilepsy (Lafora body form) II. Polyglucosans in the systemic deposits of myoclonus epilepsy and in corpora amylacea","volume":"20","author":"Sakai","year":"1970","journal-title":"Neurology"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Sullivan, M.A., Nitschke, S., Steup, M., Minassian, B.A., and Nitschke, F. (2017). Pathogenesis of Lafora Disease: Transition of Soluble Glycogen to Insoluble Polyglucosan. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18081743"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1093\/hmg\/11.11.1251","article-title":"Targeted disruption of the Epm2a gene causes formation of Lafora inclusion bodies, neurodegeneration, ataxia, myoclonus epilepsy and impaired behavioral response in mice","volume":"11","author":"Ganesh","year":"2002","journal-title":"Hum. Mol. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1093\/hmg\/ddr590","article-title":"Lafora bodies and neurological defects in malin-deficient mice correlate with impaired autophagy","volume":"21","author":"Criado","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1097\/NEN.0b013e318253350f","article-title":"Laforin and malin deletions in mice produce similar neurologic impairments","volume":"71","author":"Marinas","year":"2012","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Cabrero, A.M., S\u00e1nchez-Elexpuru, G., Serratosa, J.M., and S\u00e1nchez, M.P. (2014). Enhanced sensitivity of laforin- and malin-deficient mice to the convulsant agent pentylenetetrazole. Front. Neurosci., 8.","DOI":"10.3389\/fnins.2014.00291"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1172\/JCI13505","article-title":"Role of AMP-activated protein kinase in mechanism of metformin action","volume":"108","author":"Zhou","year":"2001","journal-title":"J. Clin. Investig."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1007\/s12035-015-9091-8","article-title":"Pharmacological Interventions to Ameliorate Neuropathological Symptoms in a Mouse Model of Lafora Disease","volume":"53","author":"Berthier","year":"2016","journal-title":"Mol. Neurobiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1007\/s13311-022-01304-w","article-title":"Early Treatment with Metformin Improves Neurological Outcomes in Lafora Disease","volume":"20","author":"Burgos","year":"2023","journal-title":"Neurotherapeutics"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1097\/WNR.0000000000000751","article-title":"4-Phenylbutyric acid and metformin decrease sensitivity to pentylenetetrazol-induced seizures in a malin knockout model of Lafora disease","volume":"28","author":"Serratosa","year":"2017","journal-title":"Neuroreport"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1186\/s13023-019-1132-3","article-title":"Treatment with metformin in twelve patients with Lafora disease","volume":"14","author":"Bisulli","year":"2019","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1111\/epi.13656","article-title":"Sodium selenate treatment improves symptoms and seizure susceptibility in a malin-deficient mouse model of Lafora disease","volume":"58","author":"Serratosa","year":"2017","journal-title":"Epilepsia"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3791","DOI":"10.1021\/acs.molpharmaceut.9b00396","article-title":"Central Nervous System Delivery and Biodistribution Analysis of an Antibody-Enzyme Fusion for the Treatment of Lafora Disease","volume":"16","author":"Austin","year":"2019","journal-title":"Mol. Pharm."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/j.cmet.2019.07.002","article-title":"Targeting Pathogenic Lafora Bodies in Lafora Disease Using an Antibody-Enzyme Fusion","volume":"30","author":"Brewer","year":"2019","journal-title":"Cell Metab."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2985","DOI":"10.1093\/brain\/awab194","article-title":"Gys1 antisense therapy rescues neuropathological bases of murine Lafora disease","volume":"144","author":"Ahonen","year":"2021","journal-title":"Brain"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1808","DOI":"10.1007\/s13311-023-01434-9","article-title":"Gys1 Antisense Therapy Prevents Disease-Driving Aggregates and Epileptiform Discharges in a Lafora Disease Mouse Model","volume":"20","author":"Donohue","year":"2023","journal-title":"Neurotherapeutics"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"107317","DOI":"10.1016\/j.eplepsyres.2024.107317","article-title":"Effect of intracerebroventricular administration of alglucosidase alfa in two mouse models of Lafora disease: Relevance for clinical practice","volume":"200","author":"Colpaert","year":"2024","journal-title":"Epilepsy Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2508","DOI":"10.1007\/s12035-021-02285-1","article-title":"Modulators of Neuroinflammation Have a Beneficial Effect in a Lafora Disease Mouse Model","volume":"58","author":"Heredia","year":"2021","journal-title":"Mol. Neurobiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2130","DOI":"10.1016\/j.ymthe.2024.05.032","article-title":"Gene therapy for Lafora disease in the Epm2a\u2212\/\u2212 mouse model","volume":"32","author":"Burgos","year":"2024","journal-title":"Mol. Ther."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1007\/s12035-019-01842-z","article-title":"Reactive Glia-Derived Neuroinflammation: A Novel Hallmark in Lafora Progressive Myoclonus Epilepsy That Progresses with Age","volume":"57","author":"Lahuerta","year":"2020","journal-title":"Mol. Neurobiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"105964","DOI":"10.1016\/j.nbd.2022.105964","article-title":"TNF and IL6\/Jak2 signaling pathways are the main contributors of the glia-derived neuroinflammation present in Lafora disease, a fatal form of progressive myoclonus epilepsy","volume":"176","author":"Rubio","year":"2023","journal-title":"Neurobiol. Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"fcac168","DOI":"10.1093\/braincomms\/fcac168","article-title":"Malin restoration as proof of concept for gene therapy for Lafora disease","volume":"4","author":"Varea","year":"2022","journal-title":"Brain Commun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1002\/ana.22156","article-title":"Glycogen hyperphosphorylation underlies lafora body formation","volume":"68","author":"Turnbull","year":"2010","journal-title":"Ann. Neurol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1093\/hmg\/ddh130","article-title":"Laforin preferentially binds the neurotoxic starch-like polyglucosans, which form in its absence in progressive myoclonus epilepsy","volume":"13","author":"Chan","year":"2004","journal-title":"Hum. Mol. Genet."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e70514","DOI":"10.1002\/ctm2.70514","article-title":"Advances in gene therapy for Lafora disease: Intravenous recombinant adeno-associated virus-mediated delivery of EPM2A and EPM2B genes","volume":"15","author":"Sciaccaluga","year":"2025","journal-title":"Clin. Transl. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2349","DOI":"10.1093\/brain\/awab110","article-title":"Astrocytic glycogen accumulation drives the pathophysiology of neurodegeneration in Lafora disease","volume":"144","author":"Duran","year":"2021","journal-title":"Brain"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3119","DOI":"10.1007\/s12035-016-9884-4","article-title":"Inflammation in Lafora Disease: Evolution with Disease Progression in Laforin and Malin Knock-out Mouse Models","volume":"54","author":"Viana","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Rom\u00e1-Mateo, C., Lorente-Pozo, S., M\u00e1rquez-Thibaut, L., Moreno-Estell\u00e9s, M., Garc\u00e9s, C., Gonz\u00e1lez, D., Lahuerta, M., Aguado, C., Garc\u00eda-Gim\u00e9nez, J.L., and Sanz, P. (2023). Age-Related microRNA Overexpression in Lafora Disease Male Mice Provides Links between Neuroinflammation and Oxidative Stress. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021089"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Gimeno, M.A., Knecht, E., and Sanz, P. (2018). Lafora Disease: A Ubiquitination-Related Pathology. Cells, 7.","DOI":"10.3390\/cells7080087"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1007\/s11064-012-0938-3","article-title":"Requirement of glycogenolysis for uptake of increased extracellular K+ in astrocytes: Potential implications for K+ homeostasis and glycogen usage in brain","volume":"38","author":"Xu","year":"2013","journal-title":"Neurochem. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/s11011-014-9524-5","article-title":"Does abnormal glycogen structure contribute to increased susceptibility to seizures in epilepsy?","volume":"30","author":"DiNuzzo","year":"2015","journal-title":"Metab. Brain Dis."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Turnbull, J., DePaoli-Roach, A.A., Zhao, X., Cortez, M.A., Pencea, N., Tiberia, E., Piliguian, M., Roach, P.J., Wang, P., and Ackerley, C.A. (2011). PTG depletion removes Lafora bodies and rescues the fatal epilepsy of Lafora disease. PLoS Genet., 7.","DOI":"10.1371\/journal.pgen.1002037"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1002\/ana.24104","article-title":"PTG protein depletion rescues malin-deficient Lafora disease in mouse","volume":"75","author":"Turnbull","year":"2014","journal-title":"Ann. Neurol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Kilkenny, C., Browne, W.J., Cuthill, I.C., Emerson, M., and Altman, D.G. (2010). Improving bioscience research reporting: The ARRIVE guidelines for reporting animal research. PLoS Biol., 8.","DOI":"10.1371\/journal.pbio.1000412"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1089\/hgtb.2014.120","article-title":"Development of a rapid, robust, and universal picogreen-based method to titer adeno-associated vectors","volume":"26","author":"Piedra","year":"2015","journal-title":"Hum. Gene Ther. Methods"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"106119","DOI":"10.1016\/j.nbd.2023.106119","article-title":"Epm2aR240X knock-in mice present earlier cognitive decline and more epileptic activity than Epm2a\u2212\/\u2212 mice","volume":"181","author":"Burgos","year":"2023","journal-title":"Neurobiol. 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