{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T22:56:34Z","timestamp":1777589794428,"version":"3.51.4"},"reference-count":55,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2019,4,25]],"date-time":"2019-04-25T00:00:00Z","timestamp":1556150400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001786","name":"University of Adelaide","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001786","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Sanfilippo syndrome (mucopolysaccharidosis type IIIA; MPS IIIA) is an inherited paediatric\u2010onset neurodegenerative disorder caused by the lysosomal deficiency of sulphamidase with subsequent accumulation of heparan sulphate. The pathological mechanisms responsible for clinical disease are unknown; however, intraneuronal accumulation of aggregation\u2010prone proteins such as \u03b1\u2010synuclein, phosphorylated tau and amyloid precursor protein suggests inefficient intracellular trafficking and lysosomal degradation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To investigate the contribution the accumulating \u03b1\u2010synuclein plays in early symptom emergence that is, impaired cognition, reduced anxiety and motor deficits, first detectable between 3\u20135\u00a0months of age.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We have crossed congenic MPS IIIA mice with \u03b1\u2010synuclein\u2010deficient (Snca<jats:sup>tm1Rosl<\/jats:sup>\/J) mice and evaluated phenotype and brain disease lesions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In a battery of behavioural tests performed on mice aged 12\u201322\u00a0weeks, we were unable to differentiate \u03b1\u2010synuclein\u2010deficient MPS IIIA mice from those with one or both copies of the \u03b1\u2010synuclein gene; all three affected genotypes were significantly impaired in test performance when compared to wild\u2010type littermates. Histological studies revealed that the rate, location and nature of deposition of other proteinaceous lesions, the disruption to endolysosomal protein expression and the inflammatory response seen in the brain of \u03b1\u2010synuclein\u2010deficient MPS IIIA mice reflected that seen in MPS IIIA mice homo\u2010 or heterozygous for \u03b1\u2010synuclein.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Deletion and\/or deficiency of \u03b1\u2010synuclein does not influence clinical and neuropathological disease progression in murine MPS IIIA, demonstrating that in and of itself, this protein does not initiate the cognitive and motor symptoms that occur in the first 5\u00a0months of life in MPS IIIA mice.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nan.12548","type":"journal-article","created":{"date-parts":[[2019,3,25]],"date-time":"2019-03-25T01:24:51Z","timestamp":1553477091000},"page":"715-731","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Early disease course is unaltered in mucopolysaccharidosis type IIIA (MPS IIIA) mice lacking \u03b1\u2010synuclein"],"prefix":"10.1111","volume":"45","author":[{"given":"K.","family":"Soe","sequence":"first","affiliation":[{"name":"Hopwood Centre for Neurobiology (HCN) South Australian Health and Medical Research Institute (SAHMRI) Adelaide SA Australia"},{"name":"Department of Paediatrics University of Adelaide Adelaide SA Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Beard","sequence":"additional","affiliation":[{"name":"Hopwood Centre for Neurobiology (HCN) South Australian Health and Medical Research Institute (SAHMRI) Adelaide SA Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Neumann","sequence":"additional","affiliation":[{"name":"Hopwood Centre for Neurobiology (HCN) South Australian Health and Medical Research Institute (SAHMRI) Adelaide SA Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P. 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