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 34 for “"hyperphosphorylation"”.
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Identification of altered Ras signaling and intermediate filament hyperphosphorylation in giant axonal neuropathy
Giant axonal neuropathy (GAN) is a rare genetic disease that causes progressive damage to the nervous system. Neurons in GAN patients develop an abnormal organization of cytoskeletal proteins called intermediate filaments (IFs), which normally provide strength and support for the overall cell …
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1, Structural and Functional Studies of Human Replication Protein A; 2 DNA Damage Responses and DNA Repair Defects in Laminopathy-Based Premature Aging.
… recognition in NER. In cells, RPA undergoes hyperphosphorylation in the N-terminus of RPA32 subunit after DNA damage. In this study, the hyperphosphorylation-induced conformational changes of RPA have been probed using mass spectrometry-based protein foot-printing, fluorescence spectroscopy …
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Studies of hyperphosphorylated tau aggregation and cytotoxicity
… of tauopathies. We found that sequential hyperphosphorylation by protein kinase A in conjugation with either glycogen synthase kinase 3b or stress-activated protein kinase 4 enabled recombinant wild-type tau of isoform 0N4R to spontaneously polymerize into small amorphous aggregates in …
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Investigation of mTOR-independent regulation of macroautophagy
… autophagy regulators undergo mitotic hyperphosphorylation, including at known repressive sites, in a manner dependent on CDK1 but not mTORC1. Indeed, we find mTORC1 is likely inactive as a result of CDK1-dependent hyperphosphorylation of RAPTOR. Thus, we conclude that mTORC1 is …
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Identification of the cellular mechanisms undelying the contribution of stress and glucocorticoids to Alzheimer's disease pathology
… the amyloid precursor protein (APP) and abnormal hyperphosphorylation of the microtubule-associated protein tau; the latter leads to cytoskeletal disruption and synaptic loss. Experiments in laboratory animals and cell systems established that stress/GC can contribute to AD pathology by triggering …
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Structural Elucidation of the Interaction Between Neurodegenerative Disease-Related Tau Protein with Model Lipid Membranes
… investigation of protein constructs and a 'hyperphosphorylation' disease mimic helped clarify the role of the microtubule binding domain in anionic lipid affinity and demonstrated even 'hyperphosphorylation' did not prevent interaction with anionic membranes. Additional studies investigated …
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TDP-43 and its role in neurodegeneration
… prone to post-translational modifications like hyperphosphorylation and aggregation, thus affecting the structure/function of TDP-43 leading to toxicity. We utilized Drosophila melanogaster as the animal model to study TDP-43 pathology. Our results show that over-expression of wild-type human …
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The Effects of Treadmill Exercise in the P301S Mouse Model of Tau Pathology
… locomotion, 2) a decrease in pathological tau hyperphosphorylation and 3) reduction of aggregated (insoluble) tau, which was confirmation of the central hypothesis. When young P301S without advanced pathology where introduced to treadmill exercise for 24 weeks, the following changes were …
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THE ROLE OF TRANSLATION ELONGATION DEFICITS IN ALZHEIMER’S DISEASE PATHOGENESIS
… from human AD patients. Instead, eEF2 exhibited hyperphosphorylation in the AD hippocampus. This phosphorylation was recapitulated in AD model mice. Phosphorylation of eEF2 at Thr 56 inhibits its function and suppresses general protein synthesis. Eukaryotic elongation factor 2 kinase (eEF2K) is …
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A streptozotocin-induced model of Alzheimer's disease in mice with wild-type human tau
… billion (Alzheimer's Association, 2012). Hyperphosphorylation of tau, the main component of neurofibrillary tangles observed in AD, leads to deficits in cell structure and function. Because recent data suggest impairments in cerebral glucose utilization and energy metabolism play a …
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Design and Synthesis of CDK-5 and MEK-5 Inhibitors and Synthesis towards Tubulysin Analogs
CDK-5 is associated with hyperphosphorylation of the microtubule-associated protein tau, formation of neurofibrillary tangles, and possibly an acceleration of the neurodegenerative progression of Alzheimer's disease. C6-O linked benzimidazoles and C-4 benzamide and phenylacetamide benzimidazoles …
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Redox Regulation of Akt Phosphorylation in PTEN-/- Mouse Embryonic Fibroblasts
… in the intracellular level of O2.- abrogated the hyperphosphorylation of Akt that was observed in these cells. Therefore, we hypothesize that O2.- may regulate the PI3K-Akt pathway not only through the inhibition of PTEN but also through a novel pathway that may be critical for the maintenance of …
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Effects of selenite on metabolic events during the proliferation of canine mammary tumor cells
… of a 46 KD protein. Selenite inhibited hyperphosphorylation of the 21, 62 and 108 KD proteins during the M phase. Results of this study suggest that perturbations in protein phosphorylation may explain the ability of selenite to alter cell proliferation.
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Design and Synthesis of Novel Benzimidazoles and Aminothiazoles as Small Molecule Inhibitors of CDK5/p25
… disease (AD). CDK5/p25 has been implicated in hyperphosphorylation of tau protein which forms neurofibrillary tangles (NFTs), a contributing factor to the pathology of Alzheimer's disease (AD). Based on the deposited X-ray crystal structure of CDK5/p25 with a non-selective CDK inhibitor …
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Using cannabidiol and trazodone to treat protein misfolding neurodegenerative disease in C. elegans
… misfolded proteins Amyloid-Beta (Aβ1-42) and/or hyperphosphorylation of Tau (p-Tau). Despite the lack of a cure for the disease, it is well known that targeting signaling pathways involved in reactive oxygen species (ROS) or the unfolded protein response (UPR) mitigates the toxic effects of …
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Inhibition of Alzheimer’s type toxic aggregates of tau with fungal secondary metabolites
… Post translational modifications such as hyperphosphorylation or truncation may induce these conformational changes and alter aggregation and function. The studies described here used in vitro assays to determine how truncation affects tau conformation and how they can alter aggregation …
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Leveraging Protein Homeostasis as a Disease-modifying Strategy
… novel mechanism connecting Aβ and tau hyperphosphorylation in Alzheimer’s disease. Additionally, comparisons of α-synuclein PN protein expressions lend support to the threshold theory in predicting regional vulnerability in the brain of Parkinson’s patients. Extending this work toward …
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Phase Separation Mediated Compartmentalisation of Rotavirus Replication
… they undergo maturation that coincides with hyperphosphorylation of NSP5. In this thesis, a minimal system comprising recombinant NSP2 and NSP5 was established, in order to study the formation of viroplasms and the effects of NSP5 phosphorylation on viral replication. This system revealed a …
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RNA Dysregulation in a Novel Human Model of TDP43 Proteinopathy
… apoptosis, microRNA dysregulation, as well as hyperphosphorylation and, likely, aggregation of TDP43. Simultaneously, the nuclear loss of TDP43 results in widespread alternative splicing errors. In a doxycycline-inducible version of this model, we demonstrate that mis-splicing occurs …
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Mechanisms of Cytokine-Induced IGF -I Insensitivity in Cancer Cells
… IGF-I-induced cyclin A accumulation and RB hyperphosphorylation. These finding demonstrates that IGF-I stimulation of E2F-1 synthesis triggers G1-S progression by inducing cyclin A and inactivating RB. Activation of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway, but not the …
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