{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:10:04Z","timestamp":1790820604197,"version":"4.1.0"},"reference-count":80,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2017,5,17]],"date-time":"2017-05-17T00:00:00Z","timestamp":1494979200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondazione Cassa di Risparmio di Padova e Rovigo - Fondazione Istituto di Ricerca Pediatrica \u201cCitt\u00e0 della Speranza\u201d","award":["Bando Ricerca Pediatrica 2012\/2014, grant #13\/09"],"award-info":[{"award-number":["Bando Ricerca Pediatrica 2012\/2014, grant #13\/09"]}]},{"name":"Brains for Brain Foundation - Onlus"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Lysosomal storage disorders (LSDs) are a group of about 50 genetic metabolic disorders, mainly affecting children, sharing the inability to degrade specific endolysosomal substrates. This results in failure of cellular functions in many organs, including brain that in most patients may go through progressive neurodegeneration. In this study, we analyzed the brain of the mouse model for Hunter syndrome, a LSD mostly presenting with neurological involvement. Whole transcriptome analysis of the cerebral cortex and midbrain\/diencephalon\/hippocampus areas was performed through RNA-seq. Genes known to be involved in several neurological functions showed a significant differential expression in the animal model for the disease compared to wild type. Among the pathways altered in both areas, axon guidance, calcium homeostasis, synapse and neuroactive ligand\u2013receptor interaction, circadian rhythm, neuroinflammation and Wnt signaling were the most significant. Application of RNA sequencing to dissect pathogenic alterations of complex syndromes allows to photograph perturbations, both determining and determined by these disorders, which could simultaneously occur in several metabolic and biochemical pathways. Results also emphasize the common, altered pathways between neurodegenerative disorders affecting elderly and those associated with pediatric diseases of genetic origin, perhaps pointing out a general common course for neurodegeneration, independent from the primary triggering cause.<\/jats:p>","DOI":"10.3390\/ijms18051072","type":"journal-article","created":{"date-parts":[[2017,5,17]],"date-time":"2017-05-17T11:13:17Z","timestamp":1495019597000},"page":"1072","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Brain RNA-Seq Profiling of the Mucopolysaccharidosis Type II Mouse Model"],"prefix":"10.3390","volume":"18","author":[{"given":"Marika","family":"Salvalaio","sequence":"first","affiliation":[{"name":"Women\u2019s and Children\u2019s Health Department, University of Padova, Via Giustiniani 3, 35128 Padova, Italy"},{"name":"Pediatric Research Institute\u2014Citt\u00e0 della Speranza, Corso Stati Uniti 4, 35127 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"D\u2019Avanzo","sequence":"additional","affiliation":[{"name":"Women\u2019s and Children\u2019s Health Department, University of Padova, Via Giustiniani 3, 35128 Padova, Italy"},{"name":"Pediatric Research Institute\u2014Citt\u00e0 della Speranza, Corso Stati Uniti 4, 35127 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0233-1677","authenticated-orcid":false,"given":"Laura","family":"Rigon","sequence":"additional","affiliation":[{"name":"Women\u2019s and Children\u2019s Health Department, University of Padova, Via Giustiniani 3, 35128 Padova, Italy"},{"name":"Pediatric Research Institute\u2014Citt\u00e0 della Speranza, Corso Stati Uniti 4, 35127 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Zanetti","sequence":"additional","affiliation":[{"name":"Women\u2019s and Children\u2019s Health Department, University of Padova, Via Giustiniani 3, 35128 Padova, Italy"},{"name":"Pediatric Research Institute\u2014Citt\u00e0 della Speranza, Corso Stati Uniti 4, 35127 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"D\u2019Angelo","sequence":"additional","affiliation":[{"name":"CRIBI Biotechnology Center, University of Padova, Viale G. 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Colombo 3, 35121 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0382-3251","authenticated-orcid":false,"given":"Maurizio","family":"Scarpa","sequence":"additional","affiliation":[{"name":"Women\u2019s and Children\u2019s Health Department, University of Padova, Via Giustiniani 3, 35128 Padova, Italy"},{"name":"Pediatric Research Institute\u2014Citt\u00e0 della Speranza, Corso Stati Uniti 4, 35127 Padova, Italy"},{"name":"Brains for Brain Foundation, Via Giustiniani 3, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosella","family":"Tomanin","sequence":"additional","affiliation":[{"name":"Women\u2019s and Children\u2019s Health Department, University of Padova, Via Giustiniani 3, 35128 Padova, Italy"},{"name":"Pediatric Research Institute\u2014Citt\u00e0 della Speranza, Corso Stati Uniti 4, 35127 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e1228","DOI":"10.1542\/peds.2008-0999","article-title":"Multidisciplinary management of Hunter syndrome","volume":"124","author":"Muenzer","year":"2009","journal-title":"Pediatrics"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1146\/annurev-cellbio-111315-125125","article-title":"The lysosome as a regulatory hub","volume":"32","author":"Perera","year":"2016","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1007\/s10545-007-0641-8","article-title":"The characterization of a murine model of mucopolysaccharidosis II (Hunter syndrome)","volume":"30","author":"Garcia","year":"2007","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1007\/s00216-016-0076-x","article-title":"Multimodal detection of GM2 and GM3 lipid species in the brain of mucopolysaccharidosis type II mouse by serial imaging mass spectrometry and immunohistochemistry","volume":"409","author":"Dufresne","year":"2017","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.ajhg.2009.07.011","article-title":"IDS crossing of the blood-brain barrier corrects CNS defects in MPS II mice","volume":"85","author":"Polito","year":"2009","journal-title":"Am. J. Hum. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1073\/pnas.252784899","article-title":"Activated microglia in cortex of mouse models of mucopolysaccharidoses I and IIIB","volume":"100","author":"Ohmi","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.ymgme.2014.12.301","article-title":"Shotgun proteomics reveals possible mechanisms for cognitive impairment in Mucopolysaccharidosis I mice","volume":"114","author":"Baldo","year":"2015","journal-title":"Mol. Genet. Metab."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Parente, M.K., Rozen, R., Cearley, C.N., and Wolfe, J.H. (2012). Dysregulation of gene expression in a lysosomal storage disease varies between brain regions implicating unexpected mechanisms of neuropathology. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0032419"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.ymgme.2016.03.003","article-title":"Integrated analysis of proteome and transcriptome changes in the mucopolysaccharidosis type VII mouse hippocampus","volume":"118","author":"Parente","year":"2016","journal-title":"Mol. Genet. Metab."},{"key":"ref_10","unstructured":"(2017, February 06). DAVID Bioinformatics Resources 6.8, Available online: https:\/\/david.ncifcrf.gov."},{"key":"ref_11","unstructured":"(2017, February 20). KOBAS 3.0. Available online: http:\/\/kobas.cbi.pku.edu.cn\/."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3852","DOI":"10.1093\/hmg\/ddr306","article-title":"Characterization of the CLEAR network reveals an integrated control of cellular clearance pathways","volume":"20","author":"Palmieri","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1523\/JNEUROSCI.4178-07.2008","article-title":"A transcriptome database for astrocytes, neurons, and oligodendrocytes: A new resource for understanding brain development and function","volume":"28","author":"Cahoy","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.tins.2009.08.002","article-title":"Molecular dissection of reactive astrogliosis and glial scar formation","volume":"32","author":"Sofroniew","year":"2009","journal-title":"Trends Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/s12035-011-8163-7","article-title":"Signaling pathways in reactive astrocytes, a genetic perspective","volume":"43","author":"Kang","year":"2011","journal-title":"Mol. Neurobiol."},{"key":"ref_16","unstructured":"Breedlove, S.M., Watson, N.V., and Rosenzweig, M.R. (2010). Biological Psychology: An Introduction to Behavioral, Cognitive, and Clinical Neuroscience, Sinauer Associates, Incorporated Publishers."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1007\/s00702-009-0240-y","article-title":"Recent advances in our understanding of neurodegeneration","volume":"116","author":"Jellinger","year":"2009","journal-title":"J. Neural Transm."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"a001941","DOI":"10.1101\/cshperspect.a001941","article-title":"Signaling from axon guidance receptors","volume":"2","author":"Bashaw","year":"2010","journal-title":"Cold Spring Harb Perspect. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.ceca.2011.03.010","article-title":"Lysosomal Ca2+ homeostasis: Role in pathogenesis of lysosomal storage diseases","volume":"50","author":"Platt","year":"2011","journal-title":"Cell Calcium"},{"key":"ref_20","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_21","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1111\/j.1471-4159.2005.03534.x","article-title":"Defective calcium homeostasis in the cerebellum in a mouse model of Niemann-Pick A disease","volume":"95","author":"Ginzburg","year":"2005","journal-title":"J. Neurochem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.nbd.2004.09.004","article-title":"Enhanced calcium release in the acute neuronopathic form of Gaucher disease","volume":"18","author":"Pelled","year":"2005","journal-title":"Neurobiol. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/1750-1326-8-23","article-title":"The synaptic maintenance problem: Membrane recycling, Ca2+ homeostasis and late onset degeneration","volume":"8","author":"Bezprozvanny","year":"2013","journal-title":"Mol. Neurodegener."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.tins.2014.06.005","article-title":"Sleep, clocks, and synaptic plasticity","volume":"37","author":"Frank","year":"2014","journal-title":"Trends Neurosci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e00401","DOI":"10.1002\/brb3.401","article-title":"Molecular neuropathology of the synapse in sheep with CLN5 Batten disease","volume":"5","author":"Amorim","year":"2015","journal-title":"Brain Behav."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1002\/jnr.23753","article-title":"Synaptic failure: The achilles tendon of sphingolipidoses","volume":"94","author":"Bongarzone","year":"2016","journal-title":"J. Neurosci. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.neuroscience.2010.02.033","article-title":"Defects of synaptic vesicle turnover at excitatory and inhibitory synapses in Niemann-Pick C1-deficient neurons","volume":"167","author":"Xu","year":"2010","journal-title":"Neuroscience"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"112","DOI":"10.15252\/emmm.201606965","article-title":"Lysosomal dysfunction disrupts presynaptic maintenance and restoration of presynaptic function prevents neurodegeneration in lysosomal storage diseases","volume":"9","author":"Sambri","year":"2017","journal-title":"EMBO Mol. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2766","DOI":"10.2174\/138161210793176572","article-title":"Neuroinflammation, oxidative stress and the pathogenesis of Alzheimer\u2019s disease","volume":"16","author":"Agostinho","year":"2010","journal-title":"Curr. Pharm. Des."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Chu-LaGraff, Q., Blanchette, C., O\u2019Hern, P., and Denefrio, C. (2010). The Batten disease Palmitoyl Protein Thioesterase 1 gene regulates neural specification and axon connectivity during Drosophila embryonic development. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0014402"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s12017-015-8382-6","article-title":"Proteomic profiling in the brain of CLN1 disease model reveals affected functional modules","volume":"18","author":"Tikka","year":"2016","journal-title":"Neuromolecular Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2153","DOI":"10.1242\/dev.044529","article-title":"Netrins: Versatile extracellular cues with diverse functions","volume":"138","author":"Correia","year":"2011","journal-title":"Development"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.ymgme.2005.05.003","article-title":"Cardiac manifestations in the mouse model of mucopolysaccharidosis I","volume":"86","author":"Jordan","year":"2005","journal-title":"Mol. Genet. Metab."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1111\/j.1600-079X.2005.00294.x","article-title":"Impairment of the melatonin rhythm in children with Sanfilippo syndrome","volume":"40","author":"Guerrero","year":"2006","journal-title":"J. Pineal Res."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Heldermon, C.D., Hennig, A.K., Ohlemiller, K.K., Ogilvie, J.M., Herzog, E.D., Breidenbach, A., Vogler, C., Wozniak, D.F., and Sands, M.S. (2007). Development of sensory, motor and behavioral deficits in the murine model of Sanfilippo syndrome type B. PLoS ONE, 2.","DOI":"10.1371\/journal.pone.0000772"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.bbr.2010.01.045","article-title":"Circadian rhythm and suprachiasmatic nucleus alterations in the mouse model of mucopolysaccharidosis IIIB","volume":"209","author":"Canal","year":"2010","journal-title":"Behav. Brain Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.bbr.2015.10.021","article-title":"Circadian profiling in two mouse models of lysosomal storage disorders; Niemann Pick type-C and Sandhoff disease","volume":"297","author":"Richardson","year":"2016","journal-title":"Behav. Brain Res."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Mazzoccoli, G., Tomanin, R., Mazza, T., D\u2019Avanzo, F., Salvalaio, M., Rigon, L., Zanetti, A., Pazienza, V., Francavilla, M., and Giuliani, F. (2013). Circadian transcriptome analysis in human fibroblasts from Hunter syndrome and impact of iduronate-2-sulfatase treatment. BMC Med. Genom., 6.","DOI":"10.1186\/1755-8794-6-37"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2368","DOI":"10.1016\/j.yexcr.2013.05.033","article-title":"Rho GTPase signaling at the synapse: Implications for intellectual disability","volume":"319","author":"Ba","year":"2013","journal-title":"Exp. Cell Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"6515","DOI":"10.1523\/JNEUROSCI.22-15-06515.2002","article-title":"Deregulation of cdk5, hyperphosphorylation, and cytoskeletal pathology in the Niemann-Pick type C murine model","volume":"22","author":"Bu","year":"2002","journal-title":"J. Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.nbd.2012.01.013","article-title":"Psychosine induces the dephosphorylation of neurofilaments by deregulation of PP1 and PP2A phosphatases","volume":"46","author":"Zhu","year":"2012","journal-title":"Neurobiol. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1093\/hmg\/ddu476","article-title":"Peripheral nerve and neuromuscular junction pathology in Pompe disease","volume":"24","author":"Falk","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2297","DOI":"10.1007\/s12035-015-9138-x","article-title":"Role of Wnt Signaling in central nervous system injury","volume":"53","author":"Lambert","year":"2016","journal-title":"Mol. Neurobiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1093\/hmg\/ddu538","article-title":"Glucocerebrosidase deficiency in zebrafish affects primary bone ossification through increased oxidative stress and reduced Wnt\/\u03b2-catenin signaling","volume":"24","author":"Zancan","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"459","DOI":"10.3389\/fnins.2016.00459","article-title":"Alzheimer disease: Crosstalk between the canonical Wnt\/\u03b2-catenin pathway and PPARs \u03b1 and \u03b3","volume":"10","author":"Vallee","year":"2016","journal-title":"Front. Neurosci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/j.bbamcr.2008.12.001","article-title":"Lysosomal disorders: From storage to cellular damage","volume":"1793","author":"Ballabio","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_47","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_48","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1146\/annurev-genet-102808-114910","article-title":"Regulation mechanisms and signaling pathways of autophagy","volume":"43","author":"He","year":"2009","journal-title":"Annu. Rev. Genet."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1038\/nn.2575","article-title":"Autophagy gone awry in neurodegenerative diseases","volume":"13","author":"Wong","year":"2010","journal-title":"Nat. Neurosci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1038\/nature05291","article-title":"The roles of intracellular protein-degradation pathways in neurodegeneration","volume":"443","author":"Rubinsztein","year":"2006","journal-title":"Nature"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/S0028-3908(03)00140-0","article-title":"Part II: \u03b1-synuclein and its molecular pathophysiological role in neurodegenerative disease","volume":"45","author":"Dev","year":"2003","journal-title":"Neuropharmacology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1046\/j.1471-4159.2002.01192.x","article-title":"The neuropathogenic contributions of lysosomal dysfunction","volume":"83","author":"Bahr","year":"2002","journal-title":"J. Neurochem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10545-013-9613-3","article-title":"Mucopolysaccharide diseases: A complex interplay between neuroinflammation, microglial activation and adaptive immunity","volume":"37","author":"Archer","year":"2014","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Ausseil, J., Desmaris, N., Bigou, S., Attali, R., Corbineau, S., Vitry, S., Parent, M., Cheillan, D., Fuller, M., and Maire, I. (2008). Early neurodegeneration progresses independently of microglial activation by heparan sulfate in the brain of mucopolysaccharidosis IIIB mice. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0002296"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Wilkinson, F.L., Holley, R.J., Langford-Smith, K.J., Badrinath, S., Liao, A., Langford-Smith, A., Cooper, J.D., Jones, S.A., Wraith, J.E., and Wynn, R.F. (2012). Neuropathology in mouse models of mucopolysaccharidosis type I, IIIA and IIIB. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0035787"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1515\/hsz-2014-0301","article-title":"Innate immune responses in the brain of sphingolipid lysosomal storage diseases","volume":"396","author":"Vitner","year":"2015","journal-title":"Biol. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1002\/jnr.21912","article-title":"Innate and adaptive immune activation in the brain of MPS IIIB mouse model","volume":"87","author":"DiRosario","year":"2009","journal-title":"J. Neurosci. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"20423","DOI":"10.1074\/jbc.R110.134452","article-title":"Common and uncommon pathogenic cascades in lysosomal storage diseases","volume":"285","author":"Vitner","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e2331","DOI":"10.1038\/cddis.2016.231","article-title":"Glial degeneration with oxidative damage drives neuronal demise in MPSII disease","volume":"7","author":"Zalfa","year":"2016","journal-title":"Cell Death Dis."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.ymgme.2011.02.016","article-title":"Oxidative stress in patients with mucopolysaccharidosis type II before and during enzyme replacement therapy","volume":"103","author":"Filippon","year":"2011","journal-title":"Mol. Genet. Metab."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.mrgentox.2011.02.005","article-title":"DNA damage in leukocytes from pretreatment mucopolysaccharidosis type II patients; protective effect of enzyme replacement therapy","volume":"721","author":"Filippon","year":"2011","journal-title":"Mutat. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.molmed.2016.12.003","article-title":"Mitochondrial dysfunction and neurodegeneration in lysosomal storage disorders","volume":"23","author":"Plotegher","year":"2017","journal-title":"Trends Mol. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.arr.2016.07.005","article-title":"The lysosomal storage disease continuum with ageing-related neurodegenerative disease","volume":"32","author":"Haslett","year":"2016","journal-title":"Ageing Res. Rev."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.1007\/s12035-014-8832-4","article-title":"Genetic convergence of Parkinson\u2019s disease and lysosomal storage disorders","volume":"51","author":"Deng","year":"2015","journal-title":"Mol. Neurobiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.nbd.2014.05.033","article-title":"Bidirectional links between Alzheimer\u2019s disease and Niemann-Pick type C disease","volume":"72","author":"Malnar","year":"2014","journal-title":"Neurobiol. Dis."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1093\/hmg\/ddl038","article-title":"Correction of Hunter syndrome in the MPSII mouse model by AAV2\/8-mediated gene delivery","volume":"15","author":"Cardone","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1111\/j.1476-5381.2009.00565.x","article-title":"Genistein reduces glycosaminoglycan levels in a mouse model of mucopolysaccharidosis type II","volume":"159","author":"Friso","year":"2010","journal-title":"Br. J. Pharmacol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"4871","DOI":"10.1093\/hmg\/ddq420","article-title":"Correction of CNS defects in the MPS II mouse model via systemic enzyme replacement therapy","volume":"19","author":"Polito","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e906","DOI":"10.1038\/cddis.2013.430","article-title":"Murine neural stem cells model Hunter disease in vitro: Glial cell-mediated neurodegeneration as a possible mechanism involved","volume":"4","author":"Zalfa","year":"2013","journal-title":"Cell Death Dis."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.ymgme.2013.09.013","article-title":"Enzyme augmentation therapy enhances the therapeutic efficacy of bone marrow transplantation in mucopolysaccharidosis type II mice","volume":"111","author":"Akiyama","year":"2014","journal-title":"Mol. Genet. Metab."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Gleitz, H.F., O\u2019Leary, C., Holley, R.J., and Bigger, B.W. (2017). Identification of age-dependent motor and neuropsychological behavioural abnormalities in a mouse model of Mucopolysaccharidosis Type II. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0172435"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1093\/bioinformatics\/btp087","article-title":"PASS: A program to align short sequences","volume":"25","author":"Campagna","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_73","unstructured":"Campagna, D., Albiero, A., Bilardi, A., Caniato, E., Forcato, C., Manavski, S., Vitulo, N., and Valle, G. (2017, February 06). PASS: A Program to Align Short Sequences. Available online: http:\/\/pass.cribi.unipd.it."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1093\/bioinformatics\/btp612","article-title":"DEGseq: An R package for identifying differentially expressed genes from RNA-seq data","volume":"26","author":"Wang","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_75","unstructured":"(2017, February 06). DEGseq: Identify Differentially Expressed Genes from RNA-seq Data. Available online: https:\/\/www.bioconductor.org\/packages\/DEGseq\/."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/nar\/gkn923","article-title":"Bioinformatics enrichment tools: Paths toward the comprehensive functional analysis of large gene lists","volume":"37","author":"Sherman","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"W720","DOI":"10.1093\/nar\/gkl167","article-title":"KOBAS server: A web-based platform for automated annotation and pathway identification","volume":"34","author":"Wu","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"D353","DOI":"10.1093\/nar\/gkw1092","article-title":"KEGG: New perspectives on genomes, pathways, diseases and drugs","volume":"45","author":"Kanehisa","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_79","unstructured":"(2017, February 09). KEGG Mapper\u2014Search & Color Pathway. Available online: http:\/\/www.kegg.jp\/kegg\/tool\/map_pathway2.html."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"22","DOI":"10.12968\/bjon.2016.25.1.22","article-title":"Management of the behavioural manifestations of Hunter syndrome","volume":"25","author":"Roberts","year":"2016","journal-title":"Br. J. Nurs."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/5\/1072\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:36:06Z","timestamp":1760207766000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/5\/1072"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,5,17]]},"references-count":80,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2017,5]]}},"alternative-id":["ijms18051072"],"URL":"https:\/\/doi.org\/10.3390\/ijms18051072","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,5,17]]}}}