ArticleProceedings of the National Academy of Sciences of the United States of America1992
Neuronal lysosomal enzyme replacement using fragment C of tetanus toxin.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1992. 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, 65 citations in OpenAlex.
- Structural flexibility of the tetanus neurotoxin revealed by crystallographic and solution scattering analyses.Journal of structural biology: X · 2021Article
- Tetanus toxin fragments and Bcl-2 fusion proteins: cytoprotection and retrograde axonal migration.BMC biotechnology · 2018Article
- Molecular dissection of botulinum neurotoxin reveals interdomain chaperone function.Toxicon : official journal of the International Society on Toxinology · 2013Review
- Lysosomal membrane permeability stimulates protein aggregate formation in neurons of a lysosomal disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- Neuronal targeting, internalization, and biological activity of a recombinant atoxic derivative of botulinum neurotoxin A.Biochemical and biophysical research communications · 2011Article
- Tetanus toxin C-fragment: the courier and the cure?Toxins · 2010Review
- Establishment of immortalized Schwann cells from Sandhoff mice and corrective effect of recombinant human beta-hexosaminidase A on the accumulated GM2 ganglioside.Journal of human genetics · 2005Article
- Enzyme replacement and enhancement therapies for lysosomal diseases.Journal of inherited metabolic disease · 2004Review
- Retargeting of adenoviral vectors to neurons using the Hc fragment of tetanus toxin.Gene therapy · 2000Article
- Protective effect of supplemental superoxide dismutase on survival of neuronal cells during starvation. Requirement for cytosolic distribution.Journal of molecular neuroscience : MN · 2000Article
- Construction of hybrid proteins that migrate retrogradely and transynaptically into the central nervous system.Proceedings of the National Academy of Sciences of the United States of America · 1997Article
- Neuropathology of mice with targeted disruption of Hexa gene, a model of Tay-Sachs disease.Acta neuropathologica · 1995Article
- Targeted disruption of the Hexa gene results in mice with biochemical and pathologic features of Tay-Sachs disease.Proceedings of the National Academy of Sciences of the United States of America · 1994Article
- Bone marrow transplantation corrects the enzyme defect in neurons of the central nervous system in a lysosomal storage disease.Proceedings of the National Academy of Sciences of the United States of America · 1994Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Development of a strategy for efficient delivery of exogenous enzyme to neuronal lysosomes is essential to achieve enzyme replacement in neurodegenerative lysosomal storage diseases. We tested whether effective lysosomal targeting of the human enzyme beta-N-acetylhexosaminidase A (Hex A; beta-N-acetyl-D-hexosaminide N-acetylhexosaminohydrolase, EC 3.2.1.52) can be obtained by coupling it via disulfide linkage to the atoxic fragment C of tetanus toxin (TTC) that is bound avidly by neuronal membrane. TTC-Hex A conjugation resulted in neuronal surface binding and enhanced endocytosis of enzyme as observed in immunofluorescence studies with rat brain cultures. In immunoelectrophoretic quantitative uptake studies, rat neuronal cell cultures contained 16- and 40-fold greater amounts of enzyme after incubation with TTC-Hex A than with nonderivatized Hex A. In cerebral cortex cell cultures from a feline model of human GM2 gangliosidosis (Tay-Sachs and Sandhoff diseases), binding and uptake patterns of the enzymes were similar to those in the rat brain cell cultures. After exposure to extracellular concentrations of enzyme attainable in vivo, lysosomal storage of immunodetectable GM2 ganglioside was virtually eliminated in neurons exposed to TTC-Hex A, whereas a minimal effect was observed with Hex A. These findings demonstrate the usefulness of TTC adducts for effective neuronal lysosomal enzyme replacement.
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