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 17 of 17 for “"lysosomal storage disorders"”.
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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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Identification of Molecular Targets for the Treatment of the Skeletal Phenotype in Lysosomal Storage Disorders
Autophagy is a lysosomal pathway deputed to the recycling of cellular components. Regulation of autophagy is essential for tissue homeostasis. The mTORC1 kinase tunes autophagy according to nutrient levels and environmental factors. Recently the laboratory in which I performed the experiments used …
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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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The Role of Progranulin in Frontotemporal Dementia
… mass spectrometry to define robust lysosomal proteomic aberrations in progranulin haploinsufficient cells in both Grn heterozygous mouse models as well as GRN-FTD patient derived fibroblasts. This led to the discovery that progranulin haploinsufficiency leads to decreases in dozens …
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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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Cytosolic sphingolipids and lysosome reactivation in neurodegenerative diseases
… an activator of vATPase, leading to proper endolysosomal acidification. Lysosomal storage disorders (LSDs), are caused by the defective activity of lysosomal proteins, including the accumulation of unmetabolized substrates. The accumulation of substrates is thought to initiate a complex …
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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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Synthesis of Bulky and Polar Galactonoamidines for the Inhibition of the Human α-Galactosidase
… numerous diseases such as cancers, diabetes, and lysosomal storage disorders, which make them important drug targets for study in medicinal chemistry. The seminal work by Pauling and Wolfenden showed that enzymes bind to their substrate at the transition state with very strong affinity. Wolfenden …
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Biophysical and Therapeutic Approaches to Neurodegenerative Disease: Insights From Lysosomal and RNA-Binding Protein Systems
… two complementary arms of this network: lysosomal quality control mediated by tripeptidyl peptidase 1 (TPP1), and RNA‑regulated proteostasis governed by the RNA‑binding protein TDP‑43. First, I reviewed general mechanisms of proteostasis disruption, highlighting how lysosomal storage …
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Engineering minimally immunogenic cargos and delivery modalities for gene therapy
… promise in the treatment of a variety of genetic disorders including retinal dystrophy, hemophilia, lysosomal storage disorders and certain types of cancer. However, there are several challenges to using CRISPR-Cas9 in the clinic, including the efficiency and specificity of the gene editing …
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Preclinical Assessment of Intravenous Gene Therapy for GM2 Gangliosidosis
… are a group of severe neurodegenerative lysosomal storage disorders characterized by the inability to catabolize GM2 Gangliosides, leading to a neurotoxic accumulation of the GM2 lipids within the central nervous system. The Hexosaminidase A (HexA) enzyme is a heterodimeric protein …
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INHIBITING THE NUCLEAR RECEPTOR ESRRA RESCUES CORE PATHOLOGIES IN CELLULAR AND ANIMAL MODELS OF BATTEN DISEASE
… disease (BD), a group of fatal neurodegenerative lysosomal storage disorders, is characterized by vision loss, cognitive decline, and seizures. Our lab recently identified the accumulation of the glycosphingolipid Gb3 as a key pathological hallmark in multiple BD subtypes (Soldati et al., 2021). …
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Examination of Abnormal Dolichol Metabolism in Infantile Batten Disease Caused by Palmitoyl Protein Thioesterase-1 (PPT1) Deficiency
… collectively as Batten disease) are a group of lysosomal storage disorders characterized by the accumulation of autofluorescent storage material in the brain. Although a number of genes underlying different forms of NCL have been cloned, the underlying mechanism for the neurodegeneration is …
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In Vivo Genome Editing: Proof of Concept in Neonatal and Adult Mouse Liver
… four different therapeutic enzymes deficient in lysosomal storage disorders. To test our hypothesis that in vivo genome editing relies on different DNA repair mechanisms in neonatal and adult mice, we applied multiple techniques including a novel reporter construct, southern blot, comparisons of …
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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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Investigating novel therapeutic approaches and targets to prevent synapse degeneration
… are important pathological targets in a range of disorders, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and lysosomal storage disorders, such as Batten disease. Loss of synaptic connections and impairments in synaptic function are present in the initial stages of …
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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 …