{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Xu T"],"funding":["Vaincre Les Maladies Lysosomales","Canadian MPS Society for Mucopolysaccharide and Related Diseases","Canadian Glycomics Network","Sanfilippo Children’s Foundation","Canadian Institutes of Health Research","NIGMS NIH HHS"],"pagination":["e177430"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12352893"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["135(16)"],"pubmed_abstract":["Mucopolysaccharidoses (MPS) are lysosomal storage diseases caused by defects in catabolism of glycosaminoglycans. MPS I, II, III, and VII, which are associated with lysosomal accumulation of heparan sulphate (HS), manifest with neurological deterioration and currently lack effective treatments. We report that neuraminidase 1 (NEU1) activity is drastically reduced in brain tissues of patients with neurological MPS and mouse models but not in neurological lysosomal disorders without HS storage. Accumulated HS disrupts the lysosomal multienzyme complex of NEU1 with cathepsin A, β-galactosidase (GLB1), and glucosamine-6-sulfate sulfatase (GALNS), leading to NEU1 deficiency and partial GLB1 and GALNS deficiencies in cortical tissues and induced pluripotent stem cell-derived (iPSC-derived) corti"],"journal":["The Journal of clinical investigation"],"pubmed_title":["Neuraminidase 1 secondary deficiency contributes to CNS pathology in neurological mucopolysaccharidoses via brain protein hypersialylation."],"pmcid":["PMC12352893"],"funding_grant_id":["R01 GM129325","Summer Studentship Research Award","Grant to A.V.P.","PJT-156345","Undergraduate Summer Research Award","PJT-180546"],"pubmed_authors":["Pan X","Dubot P","Nagar B","Sturiale L","Tomatsu S","Holley RJ","Levade T","Guo T","Ausseil J","Thiesler H","Bigger B","Pshezhetsky AV","Moore T","Garozzo D","Gorelik A","Palmigiano A","Xu T","Durcan TM","Cairo CW","Amilhon B","Rockle I","Heon-Roberts R","Khan S","Hildebrandt H"],"additional_accession":[]},"is_claimable":false,"name":"Neuraminidase 1 secondary deficiency contributes to CNS pathology in neurological mucopolysaccharidoses via brain protein hypersialylation.","description":"Mucopolysaccharidoses (MPS) are lysosomal storage diseases caused by defects in catabolism of glycosaminoglycans. MPS I, II, III, and VII, which are associated with lysosomal accumulation of heparan sulphate (HS), manifest with neurological deterioration and currently lack effective treatments. We report that neuraminidase 1 (NEU1) activity is drastically reduced in brain tissues of patients with neurological MPS and mouse models but not in neurological lysosomal disorders without HS storage. Accumulated HS disrupts the lysosomal multienzyme complex of NEU1 with cathepsin A, β-galactosidase (GLB1), and glucosamine-6-sulfate sulfatase (GALNS), leading to NEU1 deficiency and partial GLB1 and GALNS deficiencies in cortical tissues and induced pluripotent stem cell-derived (iPSC-derived) corti","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Aug","modification":"2026-05-04T15:28:42.749Z","creation":"2026-04-07T20:39:33.386Z"},"accession":"S-EPMC12352893","cross_references":{"pubmed":["40540388"],"doi":["10.1172/JCI177430"]}}