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 22 for “"Mutant Huntingtin"”.
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Silencing mutant Huntingtin by RNA interference for the treatment of Huntington Disease
… polyglutamine expansion in exon 1 of the protein huntingtin (Htt). Since the discovery of the HD mutation in 1993, various HD gene mouse models have been developed to contain either fragments or full-length copies of the mutant HD gene. The existence of these HD mouse models enables focused …
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Beyond the basal ganglia
… by a mutation in the gene encoding the protein huntingtin. Although mutant huntingtin is ubiquitously expressed throughout the body, HD research has mainly focused on the role of the basal ganglia. Dysfunction of these brain nuclei likely underlies motor disturbances in HD, including the …
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Preclinical Evaluation of Matrix Metalloproteinase Inhibitors and Protein Kinase C Activators in Cell and Mouse Models of Huntington’s Disease
… cortex results from the accumulation of toxic mutant huntingtin protein (mHTT) fragments. Full length HTT is cleaved by proteases, including caspases, calpains and matrix metalloproteinases (MMPs). Previous research has also shown altered kinase signaling pathways in HD contribute to the …
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β-cell dysfunction in Huntington's disease
… of the R6/2 mouse model we found that mutant huntingtin renders β-cells replication-deficient. This results in a reduced β-cell mass in R6/2 compared to WT mice. In addition, islet insulin content is reduced and a dramatic degranulation of β-cells is evident. As a consequence, insulin …
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Neuroprotection from the huntingtin-repressed transcriptional coactivator PGC-1α
… disorder caused by a polyglutamine repeat in the huntingtin protein which leads to degeneration of striatal and cortical tissues. PGC-1α undergoes targeted downregulation by mutant huntingtin protein (mtHtt) and PGC-1α knockout mice have striatal lesions similar to HD transgenic mice. Exogenous …
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Exploring central and enteric nervous system vulnerability in Huntington’s Disease: hints from a knock-in animal model
… currently no cure. The disease is driven by the mutant huntingtin protein, which predominantly leads to the degeneration of the striatum within the brain. Medium-sized spiny neurons (MSNs), the main neuronal components of the striatum, are selectively affected by HD, and they can be further …
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DNA Repair Deficiency in Huntington's Disease Fibroblasts and Induced Pluripotent Stem Cells
<p>Mutant huntingtin protein (mhtt)– the protein responsible for cellular dysfunction in Huntington’s disease (HD) –is a product of an expanded trinucleotide repeat (TNR) cytosine-adenine-guanine (CAG) sequence in exon 1 of the <em>huntingtin</em> <em>(HTT)</em> gene. The pathology of HD has been …
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The effects of Rhes, a striatal specific protein, on the expression of behavioral and neuropathological symptoms in a transgenic mouse model of Huntington's disease
… IT15 gene on human chromosome 4. Although the mutant huntingtin protein (mHtt) is ubiquitously expressed in HD patients, cellular degeneration occurs only in neurons within the striatum and cerebral cortex. The Ras homolog Rhes is expressed very selectively in the precise brain areas affected …
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Structural Functional Investigation of HAP40
… by an expanded CAG trinucleotide repeat in the Huntingtin (HTT) gene, resulting in a mutant huntingtin (mHTT) protein with an elongated polyglutamine tract. While the genetic basis of HD is well established, the mechanisms underlying mHTT toxicity and its impact on cellular function remain …
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Investigation of Huntingtin’s Role in DNA Repair and Transcription
… by the expansion of a CAG repeat tract in the mutant Huntingtin gene (mHTT). The mechanism of toxicity imparted by mHTT has yet to be fully elucidated, despite decades of research since its description. Research into the normal cellular function of wild type HTT has also been hindered due to …
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Cell-Type Specific Translational Profiling in Huntington's Disease Mouse Models
… in transcriptional dysfunction caused by mutant huntingtin (mhtt) have been proposed as a possible mechanism. In order to determine the differences in gene expression caused by mhtt in these two populations, we selectively isolated translated mRNAs from striatopallidal and striatonigral …
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Identification of novel palmitoyl acyl transferases and characterization of the role of Huntingtin palmitoylation in Huntington Disease
… associated synaptic scaffolding proteins. HIP14 (huntingtin interacting protein 14) is the first identified and characterized mammalian palmitoyl transferase that regulates this process. I have shown that HIP14 has striking effects on modulating trafficking and function of many proteins important …
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Aging Lowers Pex5 Levels In Cortical Neurons In Male and Female Mouse Brains
… animal model of Huntington disease (HD), where mutant huntingtin (mHtt), the causative protein in Huntington disease pathogenesis is expressed, and 3) in the cortices of aged mouse brains.</p> <p>First, we found that the rate of peroxisomes being moved to acidic lysosomes increased in a neuronal …
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Modelling Huntington’s Disease Using Direct Cell Reprogramming
… CAG repeat expansion and the production of a mutant Huntingtin protein (mHTT). There are currently no effective treatments to prevent or delay HD progression as the knowledge surrounding the specific mechanisms through which mHTT results in the preferential degeneration of striatal medium …
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Organelle specific mechanisms of neuronal cell death
… disease characterized by accumulation of mutant huntingtin protein, and causing cell death in the striatum of affected individuals, has also been shown to involve excitotoxic cell death. Intracellular organelles have been implicated in stress sensing and contribute to cell death signaling. …
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Investigating the protein quality control pathways that prevent protein aggregation in the social amoeba Dictyostelium discoideum
… found to prevent aggregation of exon 1 of the mutant huntingtin protein (Htt) in both Dictyostelium and human cells. I discovered that a region within its C-terminus, residues 61-80 (SRCP161-80), were sufficient to suppress Htt aggregation in vitro and in human cells. While I was unable to …
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Investigating neurodegenerative diseases with small molecule modulators
… of cell death caused by a pathogenic, misofolded mutant huntingtin protein in a cell culture model of Huntington's Disease (HD). These cell death inhibitors were found to target protein disulfide isomerase (PDI), an oxidoreductase known to be important in endoplasmic reticulum quality control of …
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Investigating three-dimensional (3D) gelatin methacryloyl (GelMA) hydrogel as a potential scaffold for cell transplantation in Huntington's disease
… abnormal expansion of the CAG repeats that form mutant huntingtin protein. Cell replacement therapy (CRT) offers a potential pathway to treat HD by replacing the striatal neurons lost during the disease progression with healthy ones. The emergence of cell reprogramming technology offers a …
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Identification of cellular signaling events dysregulated in Huntington’s disease.
… in the first exon of the gene encoding the Huntingtin protein (Htt) with physical, emotional, and cognitive symptoms. Current standard-of-care regimens for HD are limited to symptom-mitigating therapies with little potential for increasing the overall quality of life. As such, there is an …
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