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.
Results
Showing 1 to 20 of 38 for “"Tauopathy"”.
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Autophagy gridlock in tauopathy
… utilized the previously developed model of human tauopathy in Drosophila to examine how autophagy modulates human tau toxicity and to study the effects of human tau on the autophagic machinery. We showed that caloric restriction and rapamycin feeding suppressed the human tau-induced toxic …
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Converging Pathways: Neuroimmunology of Tauopathy and Mild Traumatic Brain Injury
… set out to map the immune responses of a primary tauopathy and repeat head injury. Using high parameter flow cytometry and RNA sequencing of spinal cords from late stage P301S tauopathy mice, I found that primary tauopathy drives a microglial transition toward an antigen-presenting phenotype as …
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The role of the microglial P2Y₆ receptor in ageing, development, and tauopathy
… memory loss. Finally, in a chronic model of tauopathy, *P2ry6⁻´⁻* mice were protected from both TAU-induced memory loss and tauopathy. The goal of this thesis was to investigate microglial-dependent mechanisms might protect *P2ry6⁻´⁻* mice from ageing- and tauopathy-induced memory loss, as …
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The role of drosophila protein kinase doubletime in circadian period determination, morning and evening oscillators and tauopathy
… part of my thesis employed a fly eye model for tauopathy to investigate whether DBT might have a role in neurodegeneration. Overexpression of the dominant negative DBTK/R enhanced the eye neurodegeneration produced by expression of human TAU in the fly eye. Our investigation suggests that DBT …
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Pre-clinical Targets for Ischemic Brain Injury
… of other diseases, such as primary age related tauopathy. Tauopathy causes demyelination/remyelination of white matter axons, potentially rendering them more susceptible to ischemic insult. This thesis has used a novel ex vivo electrophysiological model of white matter focal ischemia to analyse …
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Identify Signature Genes/Pathways to Characterize Alzheimer's Disease Subtypes Based on Uncoupled Tauopathies and Cognitive Decline
… possible underlying mechanisms. Widely spread tauopathy is one of the pathological change hallmarks in AD brains, in which microtube protein tau forms scar-like neurofibrillary tangles that kill neurons. However, subgroups of patients present unmatched tauopathy progression with their cognitive …
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Using Drosophila to study the contribution of human kinases to tau toxicity
… Moreover, in contrast with other studies, the tauopathy-associated mutation R406W on human tau did not cause an enhancement of tau-mediated degeneration of the fly eye. Selected human kinases relevant to tau pathology were tested for their ability to enhance tau toxicity in flies. Only human …
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Disease-modifying effects of human small heat shock proteins in zebrafish models of neurodegeneration
… sHSPs could ameliorate tau toxicity in zebrafish tauopathy models. Of all eleven sHSPs, HSPB1, B4 and B5 ameliorated morphological disease phenotypes induced by pan-neuronal expression of mutant A152T tau. HSPB4 and B5 have never been demonstrated to be beneficial in a tauopathy model in vivo, and …
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ROLE OF PINCH IN ABERRANT TAU PHOSPHORYLATION IN HIV CNS DISEASE
… aspects of the PINCH-signaling cascade in tauopathy are largely conserved among neurodegenerative diseases such as Alzheimer’s disease, HIV and others, the presence of the HIV protein Tat impacts specific key points in the PINCH pathway that exacerbate CNS cell dysfunction. In …
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An omics study into the molecular impact of autosomal dominant APP and MAPT mutations on the cerebral cortex
… potentially relevant to the MAPT E10+16 tauopathy in the prototype spatial transcriptomic dataset. Using bulk TMT proteomics design from a bigger cohort of patients, including patients carrying APP V717L and APP duplication mutations, I corroborate the results from the spatial …
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Antisense Reduction of the Protein Tau Attenuates Neuronal Hyperexcitability and Permits Clearance of Intraneuronal Tau Accumulations in vivo
… species, we reduced human tau in a transgenic tauopathy mouse model that develops extensive tau pathology. Following treatment with a human tau ASO, not only did reducing human tau prevent additional tau aggregates from forming, it also allowed for a striking reversal of tau accumulations and …
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Synaptic dysfunction, tau spreading, and cognitive resilience through the lens of tau oligomers in Alzheimer’s disease and related dementias
… (AD)—the most prevalent and well-characterized tauopathy. Pathological tau species are among the earliest inclusions observed in post-mortem brains of individuals with dementia and strongly correlate with cognitive decline. This work focuses on the role of the microtubule-associated protein tau, …
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Glutamate Imaging of Mouse Models of Neurodegeneration
… significantly decreased in early stages of PS19 tauopathy, glutamate levels in the dentate gyrus (DG) and cornu ammonis (CA1) increased at 9-13 months. Decreased GluCEST was concurrent with synapse loss and occurred before structural volume loss. Elevated GluCEST was associated with glial …
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The Effects of Treadmill Exercise in the P301S Mouse Model of Tau Pathology
… in a transgenic mouse model of neurodegenerative tauopathy. The central hypothesis was that endurance treadmill exercise would slow the development of neurodegenerative tau pathology and associated behavioral impairments in the P301S-tau transgenic mouse model of tauopathy. Old (7-month old) and …
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Synaptic loss in the primary tauopathies of Progressive Supranuclear Palsy and Corticobasal Degeneration
… hypothesis of connectivity-based progression of tauopathy. I further show that accrual of pathology in any given area is associated with loss of synapses, consistent with synaptic injury from tauopathy. I conclude my thesis in chapter 6, by discussing and highlighting the importance of synaptic …
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THE ROLE OF HSF1 PROTEIN REGULATION ON NEURODEGENERATION
… protein response in ER, has been implicated in tauopathy including Alzheimer’s disease (AD). The unfolded protein response (UPR) in the endoplasmic reticulum (ER) and the cytoplasmic heat stress response are two major stress response systems necessary for maintaining proteostasis for cellular …
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Análises de redes modulares de co-expressão gênica revelam vias importantes na doença de Alzheimer e paralisia supranuclear progressiva
… models, 5XFAD of amyloidopathy and TauD35 of tauopathy, we performed an integrative analysis at the gene/transcript level combined with a co-expression analysis to identify similarities and discrepancies in the biological processes affected by these two diseases. So that we could compare the …
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Advanced Bioelectronic and Microphysiological Systems for Functional Studies of Stem Cell-Derived Neural Models
… • 2D compartmentalised cultures for studying tauopathy in Alzheimer’s disease using microphysiological and bioelectronic systems; • Air-liquid interface cerebral organoids (ALI-COs), interfaced with Neuroweb, a porous, ultra-flexible microelectrode array enabling chronic electrophysiology; • …
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Prion protein in health and disease
… models of neurodegenerative disease, including Tauopathy, Parkinson's and Huntington's diseases. Deleting PrP did not substantially alter the disease phenotypes of the models that we tested, suggesting that PrP is not a major contributor to or protector against these disorders. In addition, in …
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Analysis of axonal transport and molecular chaperones during neurodegeneration in drosophila
… (Chapter 3) in a Drosophila larval model of tauopathy, in which locomotion defects are detectable under normal environmental conditions. Candidate chemical modulation of this locomotion phenotype is described that targets HSP induction (Chapter 4). The chemicals used result in no detectable …
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