ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Neuronal expression of GalNAc transferase is sufficient to prevent the age-related neurodegenerative phenotype of complex ganglioside-deficient mice.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 48 citations in OpenAlex.
- Gangliosides as Therapeutic Targets for Neurodegenerative Diseases.Journal of lipids · 2024Review
- Functional evaluation of novel variants ofFrontiers in neuroscience · 2024Article
- Rescue of GM3 synthase deficiency by spatially controlled, rAAV-mediated ST3GAL5 delivery.JCI insight · 2023Article
- Axolemmal nanoruptures arising from paranodal membrane injury induce secondary axon degeneration in murine Guillain-Barré syndrome.Journal of the peripheral nervous system : JPNS · 2023Article
- The role of gangliosides in the organisation of the node of Ranvier examined in glycosyltransferase transgenic mice.Journal of anatomy · 2022Review
- Schwann cell nodal membrane disruption triggers bystander axonal degeneration in a Guillain-Barré syndrome mouse model.The Journal of clinical investigation · 2022Article
- Complement inhibition prevents glial nodal membrane injury in a GM1 antibody-mediated mouse model.Brain communications · 2022Article
- A Compound Heterozygous Pathogenic Variant inJournal of clinical neurology (Seoul, Korea) · 2021Article
- Novel Molecular Mechanisms of Gangliosides in the Nervous System Elucidated by Genetic Engineering.International journal of molecular sciences · 2020Review
- Sialylation and Galectin-3 in Microglia-Mediated Neuroinflammation and Neurodegeneration.Frontiers in cellular neuroscience · 2020Review
- Lipids in the Physiopathology of Hereditary Spastic Paraplegias.Frontiers in neuroscience · 2020Review
- Gangliosides in the Brain: Physiology, Pathophysiology and Therapeutic Applications.Frontiers in neuroscience · 2020Review
- The Neuroimmunology of Guillain-Barré Syndrome and the Potential Role of an Aging Immune System.Frontiers in aging neuroscience · 2020Review
- Glial Sulfatides and Neuronal Complex Gangliosides Are Functionally Interdependent in Maintaining Myelinating Axon Integrity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Targeted deletion of GD3 synthase protects against MPTP-induced neurodegeneration.Genes, brain, and behavior · 2017Article
- Gangliosides of the Vertebrate Nervous System.Journal of molecular biology · 2016Review
- Anti-ganglioside antibodies are removed from circulation in mice by neuronal endocytosis.Brain : a journal of neurology · 2016Article
- PI(3,5)P2 biosynthesis regulates oligodendrocyte differentiation by intrinsic and extrinsic mechanisms.eLife · 2016Article
- C1q-targeted inhibition of the classical complement pathway prevents injury in a novel mouse model of acute motor axonal neuropathy.Acta neuropathologica communications · 2016Article
- Sialic Acid Is Required for Neuronal Inhibition by Soluble MAG but not for Membrane Bound MAG.Frontiers in molecular neuroscience · 2016Article
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
Gangliosides are widely expressed sialylated glycosphingolipids with multifunctional properties in different cell types and organs. In the nervous system, they are highly enriched in both glial and neuronal membranes. Mice lacking complex gangliosides attributable to targeted ablation of the B4galnt1 gene that encodes β-1,4-N-acetylegalactosaminyltransferase 1 (GalNAc-transferase; GalNAcT(-/-)) develop normally before exhibiting an age-dependent neurodegenerative phenotype characterized by marked behavioral abnormalities, central and peripheral axonal degeneration, reduced myelin volume, and loss of axo-glial junction integrity. The cell biological substrates underlying this neurodegeneration and the relative contribution of either glial or neuronal gangliosides to the process are unknown. To address this, we generated neuron-specific and glial-specific GalNAcT rescue mice crossed on the global GalNAcT(-/-) background [GalNAcT(-/-)-Tg(neuronal) and GalNAcT(-/-)-Tg(glial)] and analyzed their behavioral, morphological, and electrophysiological phenotype. Complex gangliosides, as assessed by thin-layer chromatography, mass spectrometry, GalNAcT enzyme activity, and anti-ganglioside antibody (AgAb) immunohistology, were restored in both neuronal and glial GalNAcT rescue mice. Behaviorally, GalNAcT(-/-)-Tg(neuronal) retained a normal "wild-type" (WT) phenotype throughout life, whereas GalNAcT(-/-)-Tg(glial) resembled GalNAcT(-/-) mice, exhibiting progressive tremor, weakness, and ataxia with aging. Quantitative electron microscopy demonstrated that GalNAcT(-/-) and GalNAcT(-/-)-Tg(glial) nerves had significantly increased rates of axon degeneration and reduced myelin volume, whereas GalNAcT(-/-)-Tg(neuronal) and WT appeared normal. The increased invasion of the paranode with juxtaparanodal Kv1.1, characteristically seen in GalNAcT(-/-) and attributed to a breakdown of the axo-glial junction, was normalized in GalNAcT(-/-)-Tg(neuronal) but remained present in GalNAcT(-/-)-Tg(glial) mice. These results indicate that neuronal rather than glial gangliosides are critical to the age-related maintenance of nervous system integrity.
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