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 23 for “"mitochondrial diseases"”.
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Pathogenesis and Therapy of Mitochondrial Diseases
… mitochondria have retained their own genome the mitochondrial DNA, mtDNA. In mammals, replication of mtDNA is ensured by the DNA polymerase POLγ, which is composed by one catalytic subunit POLγA and two accessory subunits POLγB. Mutations in the nuclear-encoded POLG gene, coding for POLγA, are a …
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Modelling and investigating treatments of childhood inherited mitochondrial diseases in zebrafish.
Mitochondrial DNA depletion syndromes (MDDS) are a group of severe, individually rare, clinically heterogeneous disorders that primarily affect children. Affected tissues tend to be those with a high energy demand such as the central nervous system and skeletal muscle. MDDS stem from disruption to …
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Developing mouse complex I as a model system: structure, function and implications in mitochondrial diseases.
… (NADH:ubiquinone oxidoreductase), located in the mitochondrial inner membrane, is a major electron entry point to the respiratory chain. It couples the energy released from electron transfer (from NADH to ubiquinone) to the concomitant pumping of protons across the membrane, to generate an …
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Applications of mitochondrial gene therapy
Genetic aberrations in the mitochondrial genome (mtDNA) can often manifest as clinical pathologies. Along with genetic mutations in nuclear encoded mitochondrial genes, these pathologies form a group of genetic disorders referred to as mitochondrial diseases. Engineered mitochondrially targeted …
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The Molecular Anatomy of Mitochondrial Disease: Identification and Characterisation of Novel Nuclear-Encoded Mitochondrial Disease Genes
Mitochondrial diseases are a group of clinically and genetically heterogeneous disorders typically associated with abnormal oxidative phosphorylation (OXPHOS). In recent years, next generation sequencing technologies have allowed for accurate genetic diagnoses of inherited mitochondrial diseases …
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Discovery and Design of NRF2 Modulators
… contributing factor of numerous inflammatory and mitochondrial diseases. The majority of current small molecule NRF2 activators are electrophilic in nature, a characteristic that may explain the prevalence of dangerous off-target effects related to these compounds. In an effort to avoid these …
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MIR-181A/B INHIBITION AS A NEW STRATEGY FOR MITOCHONDRIAL DISEASE TREATMENT
Mitochondrial diseases (MDs) are a group of rare inherited disorders caused by defective oxidative phosphorylation (OXPHOS) and defined by a wide range of clinical phenotypes. MDs show extreme genetic heterogeneity, which makes the development of efficient treatments particularly difficult. Indeed, …
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Mitochondrial Structure-Function in health and disease
Mitochondrial structure and function are inextricably linked ("structure-function"), with decrements in structure-function evident across diseases. Barriers to new therapies include a complete understanding of the underlying molecular culprits, as well as effective mitochondria-targeted therapies …
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Creating CRISPR-Cas9 genome edited iPSC lines to model a patient-specific mutation in mitochondrial disease
Mitochondrial aminoacyl tRNA-synthetases (mt-aaRS) catalyse the charging of tRNAs with their cognate amino acids in mitochondria. Mutations in mt-aaRS cause tissue-specific mitochondrial diseases, especially affecting tissues with high energy expenditure like the nervous system, heart, and kidneys. …
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Investigation into Tissue-Specific Mechanisms of Mitochondrial Dysfunction: Models of SUCLA2 Deficiency and a Screen for Potential Genetic Modifiers
With no currently effective treatments available, mitochondrial diseases are one of the most common forms of inherited multisystem disease. Primary disorders of the mitochondria affect an estimated 1 in 4,300 people with typical onset in early childhood. Mitochondrial disorders are classically …
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Investigating Cell-Type-Specific Vulnerability in Mitochondrial Disease Using Stem Cell-Derived Neuronal Models
Mitochondrial diseases are a group of widely heterogeneous genetic disorders that primarily affect tissues with high energy demands. Although disruption of oxidative phosphorylation is a shared hallmark across these conditions, their clinical manifestations display remarkable tissue specificity, …
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Mitochondrial genome engineering in the murine germline using designer nuclease technology
… are encoded in the nuclear genome. However, the mitochondrial genome, which is a circular, multi-copy genome of roughly 17 kb in size, also encodes for 13 polypeptide genes that form key components of the OXPHOS complexes, along with the 22 tRNA genes and 2 rRNA genes required for their …
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Structural and functional studies of mitochondrial NADH:ubiquinone oxidoreductase (complex I)
… the largest and most complicated enzyme in the mitochondrial electron transfer chain. It catalyses the oxidation of NADH and the reduction of ubiquinone, coupled to the translocation of protons across the mitochondrial inner membrane, maintaining the proton motive force used for ATP synthesis. …
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Modelling and correction of retinal pathologies caused by mitochondrial DNA mutations via genetic engineering
… to mutations. These mutations underlie primary mitochondrial diseases, often affecting high energy-demand tissues such as the retina, brain, heart, and skeletal muscle. Consequently, they constitute a common cause of inherited retinopathies and optic neuropathies – conditions that currently lack …
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Theoretical and Statistical Approaches to Understand Human Mitochondrial DNA Heteroplasmy Inheritance
Mitochondrial DNA (mtDNA) mutations have been widely observed to cause a variety of human diseases, especially late-onset neurodegenerative disorders. The prevalence of mitochondrial diseases caused by mtDNA mutation is approximately 1 in 5,000 of the population. There is no effective way to treat …
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Novel approaches to treat mitochondrial complex-I mediated defects in disease
Dysfunction within complex I (CI) of the mitochondrial electron transport system has been implicated in a number of disease states ranging from cardiovascular diseases to neuro-ophthalmic indications. Herein, we provide three novel approaches to model and study the impacts of injury on the function …
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Bioinformatic Approaches to Study Mitochondrial DNA Heteroplasmy
… of their own small, circular DNA, known as mitochondrial DNA(mtDNA). Mutations in mtDNA can be maternally inherited or somatic, when they occur after fertilisation. There are mechanisms at both the extra- and intracellular levels to prevent the transmission of these mutations across …
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Modelling neuronal mitochondrial aminoacyl-tRNA synthetase defects
Mitochondrial diseases cover a broad group of disorders caused by mitochondrial dysfunction, often affecting organs with high metabolic demand, such as the brain and skeletal muscle. Mutations in mitochondrial aminoacyl-tRNA synthetase (MT-ARS) genes, which are crucial for mitochondrial protein …
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Enteric and hepatic glia-like cell reactivation after astrocyte-directed twinkle helicase loss
Mitochondrial brain diseases, such as Alpers-Huttenlocher syndrome and mitochondrial recessive ataxia syndrome, are complex and severe metabolic diseases with variety of symptoms that lack any treatment. Multiple different mutations in the proteins taking part in the mitochondrial DNA (mtDNA) …
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Computer modelling of metabolic adaptions during mitochondrial dysfunction and machine learning to predict novel mitochondrial disease genes
… This thesis investigates two main causes of mitochondrial dysfunction: mitochondrial toxicity arising from side-effects of drugs; and mitochondrial diseases arising from defects in nuclear-encoded genes. Novel chemical entities being developed as drug leads are screened for cellular toxicity …
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