UID:
almafu_9961427246902883
Format:
1 streaming video file (49 min., 02 sec.) :
,
sound, color.
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004902
Series Statement:
Henry Stewart talks
Content:
Audio-visual presentation : Metabolic defect in metachromatic leukodystrophy ; Genetics ; Genotype/phenotype correlations ; Biochemical consequences of selected mutations ; Diganostic problems due to arylsulfatase A pseudodeficiency ; Gene therapy and enzyme replacement trials in an animal model.
Note:
Retrieved April 13, 2024, from https://hstalks.com/bs/50/.
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Introduction -- Outline -- MLD is a lysosomal storage disorder -- Degradation of sulfatide by ASA -- Myelin is a membrane of oligodendrocytes -- Demyelination is a pathology of MLD -- Patient suffering from MLD -- Handwriting of a MLD patient -- MLD is clinically heterogeneous -- Genetics of MLD -- Structure of the human ASA gene -- 3 mRNA generated from ASA gene -- Mutations in the human ASA gene -- Only three mutations are frequent -- Genotype-phenotype correlation in MLD -- ASA activity in fibroblasts -- Biochemical consequences of mutations -- Molecular explanations for complete activity loss -- Different types of mutations in ASA gene -- Structure of human ASA -- Many defective ASA are severely misfolded -- Molecular basis for residual ASA activity -- ASA dimers form octamers in the lysosome -- ASA forms octamers -- Pro 426 is involved in octamerization -- Consequences of Pro 426 for leucine substitution -- ASA pseudodeficiency -- Deficiency of ASA is not a proof for MLD -- Size of pseudodeficiency ASA -- Glycosylation sites in ASA pseudodeficiency -- Amount of pseudodeficiency ASA -- ASA mRNA species in pseudodeficiency -- Possible changes in mRNA species -- Structure of the ASA pseudodeficiency allele -- Diagnostic example -- Therapeutic trials in a mouse model -- Sulfatide storage in the brain of ASA deficient mice -- Sulfatide storage in glia and neurons -- Ultrastructure of storage material (1) -- Ultrastructure of storage material (2) -- ASA deficient mice do not demyelinate -- Acoustic ganglion degeneration -- Progressive neurologic symptoms -- Properties of ASA deficient mice -- Therapeutic trials in ASA knock out mice -- AAV5 ASA injections in ASA knock out mice -- Reduction of sulfatide storage after injections -- Functional improvements after injections -- Enzyme replacement studies -- Sulfatide reduction in kidney after ASA injection -- Sulfatide reduction in sciatic nerve -- CNS pathology after 4 weekly doses of ASA (1) -- CNS pathology after 4 weekly doses of ASA (2) -- Improvement of neurologic symptoms -- Summary.
Language:
English
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