{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T13:30:21Z","timestamp":1762867821562,"version":"build-2065373602"},"reference-count":90,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2019,6,28]],"date-time":"2019-06-28T00:00:00Z","timestamp":1561680000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This work explores for the first time the potential contribution of microRNAs (miRNAs) to the pathophysiology of the GM2 gangliosidosis, a group of Lysosomal Storage Diseases. In spite of the genetic origin of GM2 gangliosidosis, the cascade of events leading from the gene\/protein defects to the cell dysfunction and death is not fully elucidated. At present, there is no cure for patients. Taking advantage of the animal models of two forms of GM2 gangliosidosis, Tay-Sachs (TSD) and Sandhoff (SD) diseases, we performed a microRNA screening in the brain subventricular zone (SVZ) and striatum (STR), which feature the neurogenesis and neurodegeneration states, respectively, in adult mutant mice. We found abnormal expression of a panel of miRNAs involved in lipid metabolism, CNS development and homeostasis, and neuropathological processes, highlighting region- and disease-specific profiles of miRNA expression. Moreover, by using a computational analysis approach, we identified a unique disease- (SD or TSD) and brain region-specific (SVZ vs. STR) miRNAs signatures of predicted networks potentially related to the pathogenesis of the diseases. These results may contribute to the understanding of GM2 gangliosidosis pathophysiology, with the aim of developing effective treatments.<\/jats:p>","DOI":"10.3390\/ijms20133179","type":"journal-article","created":{"date-parts":[[2019,6,28]],"date-time":"2019-06-28T11:20:26Z","timestamp":1561720826000},"page":"3179","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Integrated Computational Analysis Highlights unique miRNA Signatures in the Subventricular Zone and Striatum of GM2 Gangliosidosis Animal Models"],"prefix":"10.3390","volume":"20","author":[{"given":"Francesco","family":"Morena","sequence":"first","affiliation":[{"name":"Department of Chemistry, Biology and Biotechnology, Biochemical and Biotechnological Sciences, University of Perugia, Perugia 06126, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vasileios","family":"Oikonomou","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Biology and Biotechnology, Biochemical and Biotechnological Sciences, University of Perugia, Perugia 06126, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Argentati","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Biology and Biotechnology, Biochemical and Biotechnological Sciences, University of Perugia, Perugia 06126, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Bazzucchi","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Biology and Biotechnology, Biochemical and Biotechnological Sciences, University of Perugia, Perugia 06126, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carla","family":"Emiliani","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Biology and Biotechnology, Biochemical and Biotechnological Sciences, University of Perugia, Perugia 06126, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9845-0370","authenticated-orcid":false,"given":"Angela","family":"Gritti","sequence":"additional","affiliation":[{"name":"San Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabata","family":"Martino","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Biology and Biotechnology, Biochemical and Biotechnological Sciences, University of Perugia, Perugia 06126, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e1233","DOI":"10.1542\/peds.2011-0078","article-title":"Natural history of infantile G(M2) gangliosidosis","volume":"128","author":"Bley","year":"2011","journal-title":"Pediatrics"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/S0065-2660(01)44072-7","article-title":"The GM2-gangliosidoses and the elucidation of the beta-hexosaminidase system","volume":"44","author":"Sandhoff","year":"2001","journal-title":"Adv. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2562","DOI":"10.1074\/jbc.M105457200","article-title":"Physiological substrates for human lysosomal beta -hexosaminidase S","volume":"277","author":"Hepbildikler","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.ymgme.2018.09.005","article-title":"Metabolomics profiling reveals profound metabolic impairments in mice and patients with Sandhoff disease","volume":"126","author":"Ou","year":"2019","journal-title":"Mol. Genet. Metab."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1016\/j.jmb.2006.04.004","article-title":"Crystallographic structure of human beta-hexosaminidase A: Interpretation of Tay-Sachs mutations and loss of GM2 ganglioside hydrolysis","volume":"359","author":"Lemieux","year":"2006","journal-title":"J. Mol. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1016\/S0022-2836(03)00216-X","article-title":"Crystal structure of human beta-hexosaminidase B: Understanding the molecular basis of Sandhoff and Tay-Sachs disease","volume":"327","author":"Mark","year":"2003","journal-title":"J. Mol. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/S0065-2660(01)44081-8","article-title":"Naturally occurring mutations in GM2 gangliosidosis: A compendium","volume":"44","author":"Mahuran","year":"2001","journal-title":"Adv. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1016\/B978-0-444-59565-2.00039-3","article-title":"Gangliosidoses","volume":"113","author":"Patterson","year":"2013","journal-title":"Handb. Clin. Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"68","DOI":"10.2174\/1566523218666180404162622","article-title":"Genetics and Therapies for GM2 Gangliosidosis","volume":"18","author":"Zaccariotto","year":"2018","journal-title":"Curr. Gene Ther."},{"key":"ref_10","first-page":"663","article-title":"The GM1 and GM2 Gangliosidoses: Natural History and Progress toward Therapy","volume":"13","author":"Regier","year":"2016","journal-title":"Pediatr. Endocrinol. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1111\/j.1471-4159.2009.05919.x","article-title":"Neural precursor cell cultures from GM2 gangliosidosis animal models recapitulate the biochemical and molecular hallmarks of the brain pathology","volume":"109","author":"Martino","year":"2009","journal-title":"J. Neurochem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2113","DOI":"10.1093\/hmg\/ddi216","article-title":"A direct gene transfer strategy via brain internal capsule reverses the biochemical defect in Tay-Sachs disease","volume":"14","author":"Martino","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1023\/A:1020256924099","article-title":"Restoration of the GM2 ganglioside metabolism in bone marrow-derived stromal cells from Tay-Sachs disease animal model","volume":"27","author":"Martino","year":"2002","journal-title":"Neurochem. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1194\/jlr.M081323","article-title":"Cerebral organoids derived from Sandhoff disease-induced pluripotent stem cells exhibit impaired neurodifferentiation","volume":"59","author":"Allende","year":"2018","journal-title":"J. Lipid Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/ng1095-170","article-title":"Mouse models of Tay-Sachs and Sandhoff diseases differ in neurologic phenotype and ganglioside metabolism","volume":"11","author":"Sango","year":"1995","journal-title":"Nat. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"111","DOI":"10.2147\/TACG.S85354","article-title":"Animal models of GM2 gangliosidosis: Utility and limitations","volume":"9","author":"Lawson","year":"2016","journal-title":"Appl. Clin. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.gpb.2012.07.005","article-title":"MicroRNAs in common human diseases","volume":"10","author":"Li","year":"2012","journal-title":"Genom. Proteom. Bioinform."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2007","DOI":"10.1002\/jcp.25854","article-title":"Interplay between miRNAs and human diseases","volume":"233","author":"Paul","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1038\/nm.2828","article-title":"Epigenetic mechanisms in neurological disease","volume":"18","author":"Jakovcevski","year":"2012","journal-title":"Nat. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.ymgme.2017.07.012","article-title":"The role of epigenetics in lysosomal storage disorders: Uncharted territory","volume":"122","author":"Hassan","year":"2017","journal-title":"Mol. Genet. Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/S0092-8674(04)00045-5","article-title":"MicroRNAs: Genomics, biogenesis, mechanism, and function","volume":"116","author":"Bartel","year":"2004","journal-title":"Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/s41580-018-0045-7","article-title":"Regulation of microRNA function in animals","volume":"20","author":"Gebert","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/nrg3198","article-title":"MicroRNA profiling: Approaches and considerations","volume":"13","author":"Pritchard","year":"2012","journal-title":"Nat. Rev. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"402","DOI":"10.3389\/fendo.2018.00402","article-title":"Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation","volume":"9","author":"Hayder","year":"2018","journal-title":"Front. Endocrinol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Morena, F., Argentati, C., Bazzucchi, M., Emiliani, C., and Martino, S. (2018). Above the Epitranscriptome: RNA Modifications and Stem Cell Identity. Genes, 9.","DOI":"10.3390\/genes9070329"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"7154","DOI":"10.1073\/pnas.1222509110","article-title":"Integrated transcriptional and competitive endogenous RNA networks are cross-regulated in permissive molecular environments","volume":"110","author":"Ala","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1038\/nrg.2016.20","article-title":"Endogenous microRNA sponges: Evidence and controversy","volume":"17","author":"Thomson","year":"2016","journal-title":"Nat. Rev. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1016\/j.bbadis.2011.02.002","article-title":"MicroRNAs and the cell cycle","volume":"1812","author":"Bueno","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.cmet.2013.06.004","article-title":"MicroRNAs and metabolism crosstalk in energy homeostasis","volume":"18","author":"Dumortier","year":"2013","journal-title":"Cell Metab."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"671","DOI":"10.2217\/epi.13.65","article-title":"Modulation of epigenetic regulators and cell fate decisions by miRNAs","volume":"5","author":"Gruber","year":"2013","journal-title":"Epigenomics"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/nri.2016.40","article-title":"MicroRNAs as regulatory elements in immune system logic","volume":"16","author":"Mehta","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.stem.2010.06.012","article-title":"MicroRNAs as regulators of differentiation and cell fate decisions","volume":"7","author":"Ivey","year":"2010","journal-title":"Cell Stem Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1038\/ncb2613","article-title":"The functions of microRNAs in pluripotency and reprogramming","volume":"14","author":"Leonardo","year":"2012","journal-title":"Nat. Cell Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/nrc3932","article-title":"MicroRNA biogenesis pathways in cancer","volume":"15","author":"Lin","year":"2015","journal-title":"Nat. Rev. Cancer"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"852","DOI":"10.15252\/emmm.201707779","article-title":"MicroRNA dysregulation in cancer: Diagnostics, monitoring and therapeutics. A comprehensive review","volume":"9","author":"Iorio","year":"2017","journal-title":"EMBO Mol. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2310","DOI":"10.1242\/dev.144337","article-title":"MicroRNAs in neural development: From master regulators to fine-tuners","volume":"144","author":"Rajman","year":"2017","journal-title":"Development"},{"key":"ref_37","first-page":"654346","article-title":"MicroRNA implications across neurodevelopment and neuropathology","volume":"2009","author":"Martino","year":"2009","journal-title":"J. Biomed. Biotechnol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/bs.ircmb.2017.04.002","article-title":"MicroRNAs in Neurodegenerative Diseases","volume":"334","author":"Quinlan","year":"2017","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.1016\/j.jmb.2019.01.046","article-title":"Emerging Role of microRNAs in Dementia","volume":"431","author":"Ramakrishna","year":"2019","journal-title":"J. Mol. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"153","DOI":"10.3389\/fgene.2019.00153","article-title":"MicroRNAs in Alzheimer\u2019s Disease","volume":"10","author":"Wang","year":"2019","journal-title":"Front. Genet."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"244","DOI":"10.3390\/genes4020244","article-title":"MicroRNAs and Molecular Mechanisms of Neurodegeneration","volume":"4","author":"Bicchi","year":"2013","journal-title":"Genes"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.2174\/138955707782331678","article-title":"RNA interference as a tool for Alzheimer\u2019s disease therapy","volume":"7","author":"Orlacchio","year":"2007","journal-title":"Mini. Rev. Med. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Ricci, C., Marzocchi, C., and Battistini, S. (2018). MicroRNAs as Biomarkers in Amyotrophic Lateral Sclerosis. Cells, 7.","DOI":"10.3390\/cells7110219"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"157","DOI":"10.2174\/2211536606666170811151503","article-title":"Environment and Neurodegenerative Diseases: An Update on miRNA Role","volume":"6","author":"Ferrante","year":"2017","journal-title":"Microrna"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1016\/j.stemcr.2017.02.012","article-title":"Synergic Functions of miRNAs Determine Neuronal Fate of Adult Neural Stem Cells","volume":"8","author":"Marzi","year":"2017","journal-title":"Stem Cell Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"58ra84","DOI":"10.1126\/scitranslmed.3001522","article-title":"Identification of hematopoietic stem cell-specific miRNAs enables gene therapy of globoid cell leukodystrophy","volume":"2","author":"Gentner","year":"2010","journal-title":"Sci. Trans. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1080\/15476286.2014.996085","article-title":"Identification of miRNAs that modulate glucocerebrosidase activity in Gaucher disease cells","volume":"11","author":"Siebert","year":"2014","journal-title":"RNA Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"D155","DOI":"10.1093\/nar\/gky1141","article-title":"miRBase: From microRNA sequences to function","volume":"47","author":"Kozomara","year":"2019","journal-title":"Nucl. Acids Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"D146","DOI":"10.1093\/nar\/gku1104","article-title":"miRDB: An online resource for microRNA target prediction and functional annotations","volume":"43","author":"Wong","year":"2015","journal-title":"Nucl. Acids Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"9975","DOI":"10.1073\/pnas.91.21.9975","article-title":"Targeted disruption of the Hexa gene results in mice with biochemical and pathologic features of Tay-Sachs disease","volume":"91","author":"Yamanaka","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Rea, P. (2015). Essential Clinical Anatomy of the Nervous System, Elsevier.","DOI":"10.1016\/B978-0-12-802030-2.00001-7"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1016\/j.cell.2014.01.044","article-title":"Neurogenesis in the striatum of the adult human brain","volume":"156","author":"Ernst","year":"2014","journal-title":"Cell"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"6627","DOI":"10.1523\/JNEUROSCI.0149-06.2006","article-title":"Subventricular zone-derived neuroblasts migrate and differentiate into mature neurons in the post-stroke adult striatum","volume":"26","author":"Yamashita","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1002\/stem.306","article-title":"Subventricular zone-derived neural progenitor cells migrate along a blood vessel scaffold toward the post-stroke striatum","volume":"28","author":"Kojima","year":"2010","journal-title":"Stem Cells"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"eaav0618","DOI":"10.1126\/sciadv.aav0618","article-title":"New neurons use Slit-Robo signaling to migrate through the glial meshwork and approach a lesion for functional regeneration","volume":"4","author":"Kaneko","year":"2018","journal-title":"Sci. Adv."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1523\/JNEUROSCI.22-03-00629.2002","article-title":"Neurogenesis in adult subventricular zone","volume":"22","year":"2002","journal-title":"J. Neurosci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.tins.2005.08.009","article-title":"Molecular regulation of adult CNS neurogenesis: An integrated view","volume":"28","author":"Hagg","year":"2005","journal-title":"Trends Neurosci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"dev156059","DOI":"10.1242\/dev.156059","article-title":"Neural stem cells: Origin, heterogeneity and regulation in the adult mammalian brain","volume":"146","author":"Obernier","year":"2019","journal-title":"Development"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"147","DOI":"10.3389\/fnana.2010.00147","article-title":"Inputs to the dorsal striatum of the mouse reflect the parallel circuit architecture of the forebrain","volume":"4","author":"Pan","year":"2010","journal-title":"Front. Neuroanat."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1002\/cne.24381","article-title":"Brain maps 4.0-Structure of the rat brain: An open access atlas with global nervous system nomenclature ontology and flatmaps","volume":"526","author":"Swanson","year":"2018","journal-title":"J. Comp. Neurol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"110","DOI":"10.4103\/1817-1745.92824","article-title":"Neuroradiological findings in GM2 gangliosidosis variant B1","volume":"6","author":"Bano","year":"2011","journal-title":"J. Pediatr. Neurosci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1007\/BF00309622","article-title":"Neuropathology of mice with targeted disruption of Hexa gene, a model of Tay-Sachs disease","volume":"89","author":"Taniike","year":"1995","journal-title":"Acta Neuropathol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1002\/cne.22153","article-title":"Effects of developmental age, brain region, and time in culture on long-term proliferation and multipotency of neural stem cell populations","volume":"517","author":"Gritti","year":"2009","journal-title":"J. Comp. Neurol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.neuroimage.2013.08.034","article-title":"Brain maturation of the adolescent rat cortex and striatum: Changes in volume and myelination","volume":"84","author":"Mengler","year":"2014","journal-title":"Neuroimage"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1038\/s41596-019-0128-8","article-title":"Protocol Update for large-scale genome and gene function analysis with the PANTHER classification system (v.14.0)","volume":"14","author":"Mi","year":"2019","journal-title":"Nat. Protoc."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/0006-8993(90)90728-T","article-title":"Distribution of ectopic neurite growth and other geometrical distortions of CNS neurons in feline GM2 gangliosidosis","volume":"510","author":"Walkley","year":"1990","journal-title":"Brain Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.bbamcr.2018.10.014","article-title":"Neurite atrophy and apoptosis mediated by PERK signaling after accumulation of GM2-ganglioside","volume":"1866","author":"Virgolini","year":"2019","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"3420","DOI":"10.1167\/iovs.05-0038","article-title":"Impaired neurite outgrowth in the retina of a murine model of Sandhoff disease","volume":"46","author":"Sango","year":"2005","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"4241","DOI":"10.1038\/ncomms5241","article-title":"Rag GTPases are cardioprotective by regulating lysosomal function","volume":"5","author":"Kim","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1034\/j.1600-0854.2000.011101.x","article-title":"Membrane traffic in sphingolipid storage diseases","volume":"1","author":"Pagano","year":"2000","journal-title":"Traffic"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"20177","DOI":"10.1074\/jbc.M106164200","article-title":"Absence of metabolic cross-correction in Tay-Sachs cells: Implications for gene therapy","volume":"277","author":"Martino","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1172\/JCI112262","article-title":"Trafficking of lysosomal enzymes in normal and disease states","volume":"77","author":"Kornfeld","year":"1986","journal-title":"J. Clin. Invest."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/j.ymgme.2011.12.012","article-title":"Mannose-6-phosphate pathway: A review on its role in lysosomal function and dysfunction","volume":"105","author":"Coutinho","year":"2012","journal-title":"Mol. Genet. Metab."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"3112","DOI":"10.1016\/j.yexcr.2009.08.016","article-title":"The inactivation of the sortilin gene leads to a partial disruption of prosaposin trafficking to the lysosomes","volume":"315","author":"Zeng","year":"2009","journal-title":"Exp. Cell Res."},{"key":"ref_75","first-page":"157","article-title":"Adult GM2 gangliosidosis: Improvement of ataxia with GABAergic drugs","volume":"17","year":"2002","journal-title":"Neurologia"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"jcs221739","DOI":"10.1242\/jcs.221739","article-title":"Lysosomal storage disorders\u07dechallenges, concepts and avenues for therapy: Beyond rare diseases","volume":"132","author":"Marques","year":"2019","journal-title":"J. Cell Sci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"29496","DOI":"10.1074\/jbc.M302964200","article-title":"Inhibition of calcium uptake via the sarco\/endoplasmic reticulum Ca2+-ATPase in a mouse model of Sandhoff disease and prevention by treatment with N-butyldeoxynojirimycin","volume":"278","author":"Pelled","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"18987","DOI":"10.1073\/pnas.0609281103","article-title":"Epidermal growth factor receptor tyrosine kinase is modulated by GM3 interaction with N-linked GlcNAc termini of the receptor","volume":"103","author":"Yoon","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1038\/s41419-017-0187-0","article-title":"EGFR activation triggers cellular hypertrophy and lysosomal disease in NAGLU-depleted cardiomyoblasts, mimicking the hallmarks of mucopolysaccharidosis IIIB","volume":"9","author":"Pezone","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1002\/cne.10578","article-title":"Insulin-like growth factor-II\/mannose-6-phosphate receptor: Widespread distribution in neurons of the central nervous system including those expressing cholinergic phenotype","volume":"458","author":"Hawkes","year":"2003","journal-title":"J. Comp. Neurol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"10954","DOI":"10.1073\/pnas.97.20.10954","article-title":"Microglial activation precedes acute neurodegeneration in Sandhoff disease and is suppressed by bone marrow transplantation","volume":"97","author":"Wada","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1152\/physrev.00033.2013","article-title":"Sialic acids in the brain: Gangliosides and polysialic acid in nervous system development, stability, disease, and regeneration","volume":"94","author":"Schnaar","year":"2014","journal-title":"Physiol. Rev."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2964","DOI":"10.1016\/j.celrep.2018.02.066","article-title":"TGF-\u00df Regulates Cathepsin Activation during Normal and Pathogenic Development","volume":"22","author":"Christian","year":"2018","journal-title":"Cell Rep."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1046\/j.1365-2990.2002.00366.x","article-title":"Lysosomal storage results in impaired survival but normal neurite outgrowth in dorsal root ganglion neurones from a mouse model of Sandhoff disease","volume":"28","author":"Sango","year":"2002","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.biomaterials.2017.08.015","article-title":"Design of a nanocomposite substrate inducing adult stem cell assembly and progression toward an Epiblast-like or Primitive Endoderm-like phenotype via mechanotransduction","volume":"144","author":"Morena","year":"2017","journal-title":"Biomaterials"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1021\/ac4023555","article-title":"A new analytical bench assay for the determination of arylsulfatase a activity toward galactosyl-3-sulfate ceramide: Implication for metachromatic leukodystrophy diagnosis","volume":"86","author":"Morena","year":"2014","journal-title":"Anal. Chem."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.biocel.2011.02.001","article-title":"Coordinated involvement of cathepsins S, D and cystatin C in the commitment of hematopoietic stem cells to dendritic cells","volume":"43","author":"Martino","year":"2011","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1038\/nmeth.3485","article-title":"miRWalk2.0: A comprehensive atlas of microRNA-target interactions","volume":"12","author":"Dweep","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"e133","DOI":"10.1093\/nar\/gku631","article-title":"The multiMiR R package and database: Integration of microRNA\u2013target interactions along with their disease and drug associations","volume":"42","author":"Ru","year":"2014","journal-title":"Nucl. Acids Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nprot.2008.211","article-title":"Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources","volume":"4","author":"Huang","year":"2009","journal-title":"Nat. Protoc."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/13\/3179\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:02:11Z","timestamp":1760187731000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/13\/3179"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,28]]},"references-count":90,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2019,7]]}},"alternative-id":["ijms20133179"],"URL":"https:\/\/doi.org\/10.3390\/ijms20133179","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2019,6,28]]}}}