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 15 of 15 for “"Lysosomal Function"”.
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Ionic Mechanism of Lysosomal Function and Cell Metabolism
<p>Two Pore Channels (TPCs) are endolysosomal ion channels that are permeable to sodium and calcium. Defects in TPCs have been implicated to impair vesicle trafficking, autophagy and cell metabolism control; however, the detailed mechanism remains largely unknown. In this study, I show that TPCs …
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The role of USP17 in lysosome trafficking and lysosomal function
… lysosome trafficking and explore the impact upon lysosomal function as well as its potential mechanism.<br/><br/>The data presented in Chapter 3 of this thesis shows the impact of USP17 upon lysosomal trafficking and lysosome-related processes. USP17 depletion affects lysosome peripheral …
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The Impact of Iron on Lysosomal Function in the Retinal Pigment Epithelium
… retina. Next, we explore the impact of iron on lysosomal function, demonstrating that iron overload leads to the accumulation of lipid-laden lysosomes in the retinal pigment epithelium. Together, our data improve our understanding of both iron homeostasis and dyshomeostasis, which can improve …
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Parkinson's Disease-Associated Protein VPS13C Regulates Phospho-Rab10-Mediated Lysosomal Function in Human iPSC-Derived Dopaminergic Neurons
… Parkinson’s disease patient care. Rare loss-of function mutations in Vacuolar Protein Sorting 13 Homolog C (VPS13C) have recently been associated with an aggressive form of early-onset Parkinson’s disease (Lesage et al., 2016). The function of VPS13C protein however remains poorly understood. …
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Lysosomal nutrients and the mTORC1 pathway
… cellular homeostasis, a better understanding of lysosomal function and metabolism and its relation to the mTOR pathway is necessary. Most components of the nutrient-sensing machinery upstream of mTORC1 localize to the lysosomal surface, and amino acids generated by lysosomes regulate mTORC1 by …
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The effects of the Parkinson’s disease-associated proteins LRRK2 and TMEM175 on the lysosomal profile of cultured mammalian cells under lysosomal stress conditions
Lysosomal dysfunction is increasingly recognised as a central factor in the development of Parkinson’s disease (PD). At least 11 out of the 24 PD-associated genes have been identified by genome-wide association studies (GWAS) to be involved in autophagy-lysosome pathways. Leucine-rich repeat kinase …
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Doxorubicin Inhibits Cardiomyocyte Autophagic Flux by Suppressing Lysosomal Acidification
… a defect in lysosome acidification. To test the functional relevance of doxorubicin-triggered autolysosome accumulation, I studied animals with diminished autophagic activity due to haploinsufficiency for Beclin 1. Beclin 1+/- mice exposed to doxorubicin manifested restored cardiac autophagic …
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Tackling Mycobacterium abscessus infection in Cystic Fibrosis
… macrophages through stimulation of autophagy and lysosomal function. I further studied over 60 chemical analogues of compound H in order to find a more active and specific compound for M. abscessus infection.
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Regional Lysosomal Malfunction Underlies the Selectivity of α-Synuclein Neurodegeneration
Dysfunction of protein homoeostasis has been implicated in the pathogenesis of a diverse array of neurodegenerative disorders. However, each neurodegenerative disease is characterized by the accumulation of particular proteins in select regions of the brain. It remains unclear how dysfunction of a …
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The role of CASM in the endolysosomal damage response
… processes such as antigen presentation. Endolysosomal (hereafter referred to as lysosomal) damage can occur in response to various cell intrinsic and extrinsic factors, such as infection, neurotoxic aggregates, and lysosomotropic drugs. Given the importance of lysosomal function to the …
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A study of the mechanism of action of novel inhibitors of tumour cell invasion
… in cells. Motuporamines cause an increase in lysosomal pH and inhibit lysosomal function, such that EGFR/EGF complexes internalized in the presence of dhMotC do not get degradad. This inhibition of EGF degradation is not dependent on Rho activity. However, the anti-invasive activity of …
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Identification of Cathepsin B and L as Novel Uva Targets Upstream of Cutaneous Lysosomal-Autophagic Dysregulation
… inactivation upstream of autophagic-lysosomal dysfunction. In human skin fibroblasts, exposure to noncytotoxic doses of chronic UVA (9.9 J/cm ², twice a week, 3 weeks) caused pronounced photooxidative impairment of cathepsin B and L enzymatic activity suppressed by antioxidant …
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INVESTIGATING THE ROLE OF SNAP29 AND THE AUTOPHAGY PATHWAY IN DROSOPHILA MELANOGASTER MODELS OF C9ORF72 - LINKED ALS/FTD.
… to disease through a dual mechanism: loss of function of the C9orf72 gene and/or toxic gain of function mediated by the repeat RNA and toxic dipeptide repeats (DPRs) generated from the G4C2 expansion itself. While G4C2 toxicity has been implicated in impairing various cellular processes, its …
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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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Fluorescence lifetime imaging microscopy to study protein aggregation in the context of neurodegenerative diseases
… overrides any contribution from mitochondrial dysfunction. For a better understanding of heat dissipation from Aβ peptides, classical molecular dynamic simulations are performed. It is shown that heat retention by an Aβ peptide is promoted under intracellular-mimicking conditions due to fewer …