Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 16 of 16 for “"lysosomal storage disorder"”.
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The role of heterozygous lysosomal storage disorder alleles as risk factors for dementia
… systems are believed to be involved. Of these, lysosomal network dysfunction is an increasingly recognised pathogenic factor. Lysosomal network disruptions, including upregulated endocytosis, aberrant trafficking and storage of undegraded substrates, commence from the earliest stages of …
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The analysis of a mouse model of Lysosomal Storage Disorder uncovers a role for astrocyte dysfunction in neurodegeneration
… Multiple Sulfatase Deficiency (MS D), a severe Lysosomal Storage Disorder (LSD) caused by mutations in the Sulfatase Modifying Factor 1 (SUMF1) gene. Using Cre/Lox mouse models, I found that astrocyte-specific deletion of Sumf1 in vivo induced severe lysosomal storage and autophagy dysfunction …
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C. elegans apoptosis : CED-4 translocation and involvement in a model of mucolipidosis type IV human lysosomal storage disorder
… type IV gene, which is mutated in a lysosomal storage disorder. We found that cup-5 is required for viability and that excess lysosomes accumulate in cup-5 mutants. In addition, cup--5 mutants contain excess programmed cell deaths, suggesting that apoptosis may play a role in the …
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Modelling saposin deficiency in Drosophila: progressive neurodegeneration, storage and physiological decline
Saposin deficiency is a lysosomal storage disorder (LSD) characterised by the lysosomal accumulation of sphingolipids. The disorder is caused by mutations in the prosaposin gene, which encodes 4 activator proteins: saposins A - D. Mutations affecting individual saposins lead to different LSDs. …
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Molecular characterization of ovine GM1 gangliosidosis
… GM1-gangliosidosis is an autosomal recessive lysosomal storage disorder. Affected lambs are born relatively normal, however at approximately four months of age they begin exhibiting severe neurological symptoms. Pathology progresses rapidly in affected lambs ultimately resulting in death by …
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No Difference In Health Related Quality of Life Between Therapeutic Options For Type 1 Gaucher Disease
<p>Type 1 Gaucher disease (GD) is the most common lysosomal storage disorder. Previously, treatment for GD was limited to intravenous enzyme replacement therapy (ERT). ERT reduces symptoms and increases healthrelated quality of life (HRQoL) in people with this condition. In 2014, oral substrate …
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The Role of Astrocyte Activation in Infantile Neuronal Ceroid Lipofuscinosis
… Disease, is an inherited neurodegenerative lysosomal storage disorder affecting the central nervous system: CNS) during infancy or childhood. Hallmark pathological changes include accumulation of autofluorescent material, neuronal loss, cortical thinning, and brain atrophy, which ultimately …
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Engineering cell-based micropharmacies for in vivo protein replacement therapy
The treatment of many chronic and genetic disorders depends on the consistent delivery of therapeutic proteins to correct underlying deficiencies or modulate disease progression. However, conventional methods, such as enzyme replacement therapy (ERT) and cancer immunotherapies, often require …
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Developmental Characterization of the Choroid Plexus in Sialidosis (Neu1 Deficient) Mice
<p>The lysosomal sialidase Neuraminidase-1 (Neu1) initiates the hydrolysis of sialoglycoconjugates by cleaving their terminal sialic acid residues. Neu1 creates a complex with the carboxypeptidase protective protein/cathepsin A (PPCA), which is necessary for its catalytic activation and its …
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Evaluation of Select Publicly Available in Silico Methods for Predicting Functional Effects of Missense Mutations in the GALNS Gene
… Morquio A (MPS IVA), a rare, autosomal recessive lysosomal storage disorder (LSD) caused by a deficiency of lysosomal enzyme N-acetylgalactosamine-6-sulfatase (GALNS). In the severe form of the disease, life expectancy is less than 30 years. More than 200 unique missense mutations have been …
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Development of a Cellular Model for Morquio A Syndrome
… IVA (MPS IVA; Morquio A), is a lysosomal storage disorder characterized by the deficiency of N-acetylgalactosamine-6-sulfatase (GALNS), resulting in the accumulation of glycosaminoglycans (GAGs) such as keratan sulfate (KS) (Northover et al., 1996) and chondroitin-6-sulfate. …
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Phenotypic characterisation of human iPSC neuronal models of GM2 gangliosidoses
… the effects of their accumulation in ganglioside lysosomal storage disorders (LSD). The GM2 gangliosidoses Tay-Sachs and Sandhoff disease are a type of LSD, resulting from the inability of the lysosome to catabolise the breakdown of the ganglioside GM2. This is due to a loss or mutation of either …
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ADVANCED AAV-MEDIATED LIVER-DIRECTED GENE THERAPIES FOR HAEMOPHILIA A AND MUCOPOLYSACCHARIDOSIS TYPE VI
… A (HemA), the most common X-linked bleeding disorder (affecting 1 in 5,000 males), caused by a deficiency of clotting factor 8 (F8, ~7 kb). I first demonstrated the successful full-length reconstitution of the large (~5 kb) and highly active B-domain deleted (B-DD) N6-F8 variant in vitro. …
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TRPML1: Role In Autophagy And Potential Target To Treat Lysosomal Storage Disorders
… control of cell function. Here we show that a lysosomal Ca2+ signaling mechanism controls the activities of the phosphatase calcineurin and of its substrate TFEB, a master transcriptional regulator of lysosomal biogenesis and autophagy. Lysosomal Ca2+ release via mucolipin 1 (TRPML1) activates …
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Mammalian Cell Line Development Platform for Recombinant Protein Production: Expanding the Protein Expression Toolbox for Research and Drug Discovery Applications
… therapeutics to treat rare diseases including lysosomal storage disorders (LSDs), a group of about 50 individually rare disorders together affecting 1 in 8,000 live births. With an increase in the number of novel therapeutics in our drug discovery pipeline, there is a high demand to produce a …
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Characterization Of The Skeletal Phenotype In Idua-W392X Knock-In Mice: Bone Metabolism Biomarkers
… Type I (MPS I, Hurlers Syndrome) is a lysosomal storage disease caused by a deficiency of alpha-L-iduronidase (IDUA). IDUA catalyzes the degradation of the two glycosaminoglycans (GAGs); heparin sulfate (HS) and demantan sulfate (DS). The accumulation of HS and DS makes MPS I …