ArticleThe Journal of experimental medicine2022
Glucosamine amends CNS pathology in mucopolysaccharidosis IIIC mouse expressing misfolded HGSNAT.
Article in The Journal of experimental medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 32 citations in OpenAlex.
- Advances in Therapies for Mucopolysaccharidoses.Current issues in molecular biology · 2026Review
- Modelling synaptic dysfunction in childhood dementia using human iPSC-derived cortical networks.Nature communications · 2026Article
- Integrated multi-omics profiling identifies genetic loci of African swine fever resistance in pigs.GigaScience · 2026Article
- HGSNAT alleviates oxygen-glucose deprivation- induced endothelial injury by suppressing ER stress: implications for Moyamoya disease.Frontiers in molecular neuroscience · 2026Article
- Cathepsin B inhibition blocks amyloidogenesis in the mouse models of neurological lysosomal diseases MPS IIIC and sialidosis.Molecular therapy. Methods & clinical development · 2025Article
- Extracellular vesicles from microglial cells activated by abnormal heparan sulfate oligosaccharides from Sanfilippo patients impair neuronal dendritic arborization.Molecular medicine (Cambridge, Mass.) · 2024Article
- Structure and mechanism of lysosome transmembrane acetylation by HGSNAT.Nature structural & molecular biology · 2024Article
- Structure of the human heparan-α-glucosaminideeLife · 2024Article
- Structure of the human heparan-α-glucosaminidebioRxiv : the preprint server for biology · 2024Article
- Article
- Severe kidney dysfunction in sialidosis mice reveals an essential role for neuraminidase 1 in reabsorption.JCI insight · 2023Article
- Histological characterization of retinal degeneration in mucopolysaccharidosis type IIIC.Experimental eye research · 2023Article
- Pharmacological Chaperones and Protein Conformational Diseases: Approaches of Computational Structural Biology.International journal of molecular sciences · 2023Review
- Severe central nervous system demyelination in Sanfilippo disease.Frontiers in molecular neuroscience · 2023Article
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 3 countries.
Funding
Abstract
The majority of mucopolysaccharidosis IIIC (MPS IIIC) patients have missense variants causing misfolding of heparan sulfate acetyl-CoA:α-glucosaminide N-acetyltransferase (HGSNAT), which are potentially treatable with pharmacological chaperones. To test this approach, we generated a novel HgsnatP304L mouse model expressing misfolded HGSNAT Pro304Leu variant. HgsnatP304L mice present deficits in short-term and working/spatial memory 2-4 mo earlier than previously described constitutive knockout Hgsnat-Geo mice. HgsnatP304L mice also show augmented severity of neuroimmune response, synaptic deficits, and neuronal storage of misfolded proteins and gangliosides compared with Hgsnat-Geo mice. Expression of misfolded human Pro311Leu HGSNAT protein in cultured hippocampal Hgsnat-Geo neurons further reduced levels of synaptic proteins. Memory deficits and majority of brain pathology were rescued in mice receiving HGSNAT chaperone, glucosamine. Our data for the first time demonstrate dominant-negative effects of misfolded HGSNAT Pro304Leu variant and show that they are treatable by oral administration of glucosamine. This suggests that patients affected with mutations preventing normal folding of the enzyme can benefit from chaperone therapy.
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Registered trials
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