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 20 of 39 for “"PINK1"”.
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Brain Inflammation Regulated by PINK1
… of dopaminergic neurons in the substantia nigra. PINK1 is a well-known autosomal recessive familial PD gene, expressed in both neurons and glia. In this study, I analyzed the roles of PINK1 in brain inflammation using slice cultures prepared from PINK1 knockout (KO) and wild type (WT) mice since …
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MECHANISM OF PINK1-MEDIATED UBIQUITIN PHOSPHORYLATION
Ubiquitin phosphorylation by PINK1 (PTEN-induced Putative Kinase 1) is crucial for mitochondrial quality control and loss or mutation of PINK1 can lead to autosomal recessive juvenile parkinsonism (AR-JP). PINK1 is an unusual kinase, as it is characterised by three unique insertions in its kinase N …
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The mechanism of Parkin activation by PINK1 phosphorylation
… Ub ligase Parkin (PARK2) and the protein kinase PINK1 (PARK6) are genetically linked to Young-Onset Parkinson’s Disease. The two enzymes orchestrate clearance of damaged, cytotoxic mitochondria through a specialized form of autophagy termed mitophagy. By phosphorylating ubiquitin (Ub) on the …
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Regulation of the Parkin E3 ligase by PINK1-dependent phosphorylation
… by autoinhibitory intramolecular interactions. PINK1 is a mitochondrial Ser/Thr kinase that is unique in possessing a N-terminal mitochondrial targeting sequence and three loop insertions within its kinase domain. At the outset of my PhD, PINK1 was discovered to phosphorylate Parkin at Serine 65 …
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Investigating the function of PINK1 in cancer development and pathogenesis
PTEN‐induced kinase 1 (PINK1) was identified initially in cancer cells as a gene up‐regulated by overexpression of the central tumour suppressor, PTEN. Loss‐of‐function mutations in PINK1 were discovered subsequently to cause autosomal recessive Parkinsonʹs disease (ARPD). Despite much research …
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Analysis of PINK1/Parkin-related mitochondrial quality control in Drosophila
… (PD), Parkin, a cytosolic ubiquitin ligase, and PINK1, a mitochondrially targeted kinase, have been shown to play key roles in this mitophagy. However, little is known about their impact on basal mitophagy in vivo. Moreover, while the consequences of mitophagy defects and the mechanisms that lead …
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Advancing understanding of endogenous PINK1-Parkin signalling linked to Parkinson’s disease
… dysfunction with PD. Two of these gene products, PINK1 and Parkin, function together in a common pathway. The PINK1 kinase acts as a sensor for mitochondrial damage, catalysing downstream phosphorylation of both Parkin and ubiquitin (Ub) at Ser65, thereby activating Parkin E3 Ub ligase activity. …
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Investigating the role of PINK1-dependent Rab signalling in Parkinson's disease
… cascades that may contribute to PD pathology. PINK1 is mutated in early-onset forms of PD, and its downstream signalling cascade is the main focus of this thesis. <br/><br/>PINK1 was previously demonstrated to phosphorylate downstream substrates, Parkin and ubiquitin at Ser65, whilst also …
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Investigating the mechanisms by which PINK1 protects against Parkinson's disease
PINK1 (PTEN-induced putative kinase-1) functions as a ubiquitous serine-threonine kinase, with pro-survival, neuroprotective and anti-stress signalling functions. Autosomal recessive mutations in PINK1, resulting in a loss of PINK1 function, cause early onset Parkinson’s disease (PD). This thesis …
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Exploring Parkinson’s disease associated LRRK2 and PINK1/Parkin signal transduction pathways within immune cells
… familial forms of the disease2. LRRK2 and PINK1 are two independent genes that respectively cause autosomal dominant and autosomal recessive forms of PD. They both encode protein kinases, which control signal transduction pathways through reversible phosphorylation of target proteins3. …
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Biochemical characterisation of the Parkinson's disease-associated kinase PINK1: Insights from the insect world
… to mutations in known genes, one of which is the PINK1 gene, first linked to PD a decade ago. Since then, over 30 mutations in PINK have been described. The PINK1 gene encodes an unusual serine/threonine protein kinase; uniquely among protein kinases, PINK1 is anchored to the mitochondria and …
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Determination of the Composition and Architecture of the Mitochondrial Ubiquitome in PINK1/Parkin Mitophagy
… underlie the etiology of the disease. The kinase PINK1, and the ubiquitin (Ub) E3 ligase Parkin, function in a pathway to maintain mitochondrial quality control through the engulfment of mitochondria by the autophagy system, in a process termed mitophagy. Through a positive feedback loop centred …
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Investigating the role of the Nrf2-Keap1 pathway in mitophagy
… mitophagy pathways have been discovered with the PINK1-Parkin pathway being most investigated. PINK1-Parkin mediated mitophagy occurs in stress-induced conditions. Interestingly, another pathway, the Nrf2-Keap1 pathway, which acts as sensor for stress within the cell, is also activated and …
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In vivo and in vitro approaches to characterising axon growth and metabolic alterations in Parkinson’s disease
… degeneration in this neurodegenerative disease. PINK1 is a mitochondrial kinase that ensures mitochondrial health and mutations in PINK1 cause PD. My work explored how mutations in PINK1 alter cellular metabolism, using a Drosophila model of PD. Multi-omics analysis of pink1 mutant flies …
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THE ORGANIZATION OF MITOCHONDRIAL QUALITY CONTROL AND LIFE CYCLE IN THE NERVOUS SYSTEM IN VIVO IN THE ABSENCE OF PINK1
Maintenance of healthy mitochondria is crucial in cells, such as neurons, with high
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Microbiome-Brain interactions in Parkinson’s neurodegeneration: The effect of microbiota modulation in a PINK1 mutant Drosophila melanogaster model of Parkinson’s disease
… fly strains, a wildtype control (W1118) and a PINK1B9 mutant as a model of PD and tested the effect of four strains of bacteria: Lactobacillus acidophilus, Enterococcus faecalis, Escherichia coli and Enterobacter cloacae. We started by investigating the difference between the two models without …
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Be Eaten to Stay Healthy: Elucidating the Mechanisms of Mitochondrial Quality Control by Mitophagy
… and tensin homolog-induced putative kinase 1 (PINK1) and Parkin have been identified as important regulators of mitophagy in mammalian cells, directly linking mitophagy to neurodegeneration. The role of these two proteins in this mitophagy is further explored in the first part of this …
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