Heparan sulfate binding protein treatment ameliorates neuropathology and behavioral abnormalities in mucopolysaccharidosis IIIB mice
Abstract Mucopolysaccharidosis IIIB (MPS IIIB) is a metabolic neurodegenerative disorder caused by a deficiency of the lysosomal enzyme α-N-acetylglucosaminidase (NAGLU), which is involved in the degradation of heparan sulfate (HS). Affected patients exhibit progressive neurodegeneration, behavioral...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-08-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-025-02648-w |
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| author | Serenella Anzilotti Melania Scarcella Mariangela Ciampa Noemi Di Muraglia Camilla Anastasio Chiara Fiorentino Federica Rossin Luigi Avallone Giuseppe Pignataro Luigi Michele Pavone Valeria De Pasquale |
| author_facet | Serenella Anzilotti Melania Scarcella Mariangela Ciampa Noemi Di Muraglia Camilla Anastasio Chiara Fiorentino Federica Rossin Luigi Avallone Giuseppe Pignataro Luigi Michele Pavone Valeria De Pasquale |
| author_sort | Serenella Anzilotti |
| collection | DOAJ |
| description | Abstract Mucopolysaccharidosis IIIB (MPS IIIB) is a metabolic neurodegenerative disorder caused by a deficiency of the lysosomal enzyme α-N-acetylglucosaminidase (NAGLU), which is involved in the degradation of heparan sulfate (HS). Affected patients exhibit progressive neurodegeneration, behavioral disturbances, and a shortened lifespan. Currently, there is no effective treatment for MPS IIIB. We have recently developed a new therapeutic strategy based on the use of the HS-binding protein NK1, a spliced variant of hepatocyte growth factor. Here, we demonstrate that treating Naglu −/− mice with recombinant NK1 ameliorates neuropathology by reducing HS storage, lysosomal dysfunction, autophagy imbalance, and neuroinflammation in the cortex and hippocampus of MPS IIIB mouse brains. Furthermore, we found that recombinant NK1 treatment improves cognitive behavior and motor activity in Naglu −/− mice, as assessed using open field, object recognition, and T-maze tests. Our findings suggest that recombinant NK1 is a promising candidate for the treatment of MPS IIIB and other lysosomal storage diseases associated with central nervous system dysfunction. |
| format | Article |
| id | doaj-art-9eeb01cec1b84d7894bcfdebf2671760 |
| institution | Kabale University |
| issn | 2058-7716 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj-art-9eeb01cec1b84d7894bcfdebf26717602025-08-20T03:45:45ZengNature Publishing GroupCell Death Discovery2058-77162025-08-0111111010.1038/s41420-025-02648-wHeparan sulfate binding protein treatment ameliorates neuropathology and behavioral abnormalities in mucopolysaccharidosis IIIB miceSerenella Anzilotti0Melania Scarcella1Mariangela Ciampa2Noemi Di Muraglia3Camilla Anastasio4Chiara Fiorentino5Federica Rossin6Luigi Avallone7Giuseppe Pignataro8Luigi Michele Pavone9Valeria De Pasquale10Department of Human Sciences and Quality of Life Promotion, San Raffaele UniversityDepartment of Molecular Medicine and Medical Biotechnology, Medical School, University of Naples Federico IIDepartment of Molecular Medicine and Medical Biotechnology, Medical School, University of Naples Federico IIDivision of Pharmacology, Department of Neuroscience, Reproductive and Dentistry Sciences, Medical School, University of Naples Federico IIDepartment of Precision Medicine, University of Campania Luigi VanvitelliDepartment of Molecular Medicine and Medical Biotechnology, Medical School, University of Naples Federico IIDepartment of Veterinary Medicine and Animal Production, University of Naples Federico IIDepartment of Veterinary Medicine and Animal Production, University of Naples Federico IIDivision of Pharmacology, Department of Neuroscience, Reproductive and Dentistry Sciences, Medical School, University of Naples Federico IIDepartment of Molecular Medicine and Medical Biotechnology, Medical School, University of Naples Federico IIDepartment of Veterinary Medicine and Animal Production, University of Naples Federico IIAbstract Mucopolysaccharidosis IIIB (MPS IIIB) is a metabolic neurodegenerative disorder caused by a deficiency of the lysosomal enzyme α-N-acetylglucosaminidase (NAGLU), which is involved in the degradation of heparan sulfate (HS). Affected patients exhibit progressive neurodegeneration, behavioral disturbances, and a shortened lifespan. Currently, there is no effective treatment for MPS IIIB. We have recently developed a new therapeutic strategy based on the use of the HS-binding protein NK1, a spliced variant of hepatocyte growth factor. Here, we demonstrate that treating Naglu −/− mice with recombinant NK1 ameliorates neuropathology by reducing HS storage, lysosomal dysfunction, autophagy imbalance, and neuroinflammation in the cortex and hippocampus of MPS IIIB mouse brains. Furthermore, we found that recombinant NK1 treatment improves cognitive behavior and motor activity in Naglu −/− mice, as assessed using open field, object recognition, and T-maze tests. Our findings suggest that recombinant NK1 is a promising candidate for the treatment of MPS IIIB and other lysosomal storage diseases associated with central nervous system dysfunction.https://doi.org/10.1038/s41420-025-02648-w |
| spellingShingle | Serenella Anzilotti Melania Scarcella Mariangela Ciampa Noemi Di Muraglia Camilla Anastasio Chiara Fiorentino Federica Rossin Luigi Avallone Giuseppe Pignataro Luigi Michele Pavone Valeria De Pasquale Heparan sulfate binding protein treatment ameliorates neuropathology and behavioral abnormalities in mucopolysaccharidosis IIIB mice Cell Death Discovery |
| title | Heparan sulfate binding protein treatment ameliorates neuropathology and behavioral abnormalities in mucopolysaccharidosis IIIB mice |
| title_full | Heparan sulfate binding protein treatment ameliorates neuropathology and behavioral abnormalities in mucopolysaccharidosis IIIB mice |
| title_fullStr | Heparan sulfate binding protein treatment ameliorates neuropathology and behavioral abnormalities in mucopolysaccharidosis IIIB mice |
| title_full_unstemmed | Heparan sulfate binding protein treatment ameliorates neuropathology and behavioral abnormalities in mucopolysaccharidosis IIIB mice |
| title_short | Heparan sulfate binding protein treatment ameliorates neuropathology and behavioral abnormalities in mucopolysaccharidosis IIIB mice |
| title_sort | heparan sulfate binding protein treatment ameliorates neuropathology and behavioral abnormalities in mucopolysaccharidosis iiib mice |
| url | https://doi.org/10.1038/s41420-025-02648-w |
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