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 19 of 19 for “"polyQ"”.
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Physiological and pathological role of serine 96 phosphorylation in the regulation of androgen receptor
… of a CAG tandem repeat encoding a polyglutamine (polyQ) tract in the androgen receptor (AR) gene. SBMA belongs to the family of polyQ diseases, which includes eight other neurological diseases caused by the same mutation in unrelated genes. PolyQ diseases share common features, such as that polyQ …
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Factors modifying the aggregation of atrophin-1 acting in cis and in trans
Ten polyQ (polyglutamine) diseases constitute a group of hereditary, neurodegenerative, lethal disorders, characterized by neuronal loss and motor and cognitive impairments. The only common molecular feature of polyQ disease-associated proteins is the homopolymeric polyglutamine repeat. The …
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Regulation of the redox homeostasis during polyglutamine misfolding in Huntington’s Disease
… cellular models of intracellular polyglutamine (polyQ) protein misfolding were established for mechanistic studies.<br/><br/>Various in vitro transient and stable cell expression systems expressing an N-terminal fragment of huntingtin (htt) (httExon 1, httEx1) with/or without a polyQ expansion …
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Biological Consequences of Polyglutamine Repeats in Drosophila Muscle
Polyglutamine (polyQ) disease occurs by CAG repeat expansion, encoding a glutamine tract in the affected protein. Accumulation of these mutant polyQ proteins leads to formation of insoluble protein aggregates that impair many vital cellular processes. This manifests in neurodegenerative symptoms …
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The Role of Microglia and Astrocyte in Spinocerebellar Ataxia Type 1
… on the effect of the disease-causing protein, a polyQ expanded ATAXIN-1 (ATXN1) on neurons, the relative contribution to disease of glia has been unknown. Here I present my work on glial-neuron interactions in the context of SCA1; focusing on the neuroinflammatory and activation of microglia as …
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Investigating the protein quality control pathways that prevent protein aggregation in the social amoeba Dictyostelium discoideum
… an organism resistant to polyglutamine (polyQ) protein aggregation and whose proteostasis pathways have not been intensively studied. Serine- rich chaperone protein 1 (SRCP1), a Dictyostelium-specific chaperone, was previously found to prevent aggregation of exon 1 of the mutant …
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Protein misfolding toxicity and inclusion formation in cellular models of neurodegeneration
… lateral sclerosis (ALS) and polyglutamine (polyQ) expanded huntingtin, which causes Huntington’s disease (HD). Genetic, biochemical, and pathological findings implicate RGNEF and Matrin3 in Amyotrophic Lateral Sclerosis (ALS). In this thesis we establish two novel humanized yeast models to …
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Characterization of a Drosophila model of Huntington's disease
… neurological disorder caused by a polyglutamine (polyQ) repeat expansion in the huntingtin (Htt) protein. The disease is characterized by neurodegeneration and formation of neuronal intracellular inclusions primarily in the striatum and cortex, leading to personality changes, motor impairment, and …
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Modulation of Huntington's disease-associated phenotypes by the striatal-enriched transcription factor Foxp2
… (HTT) gene, which encodes a poly-glutamine (polyQ) repeat protein. Despite widespread expression of the HTT gene, HD presents with massive neuronal cell loss and transcriptional dysregulation primarily in the striatum and deep layers of the cortex. Synaptic dysfunction and motor deficits are …
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Defining The Functions of Usp22 and Usp44 In Regulation of H2Bub1 Levels
… ataxia type 7 (SCA7), due to a polyglutamine (polyQ) expansion in its N-terminal region. Given the allosteric regulation of USP22 DUB activity within the DUBm, whether and how the polyQ expansion in ATXN7 affects SAGA DUB activity was not known. To address this question, we reconstituted the …
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AR-A IPSCS: GENERATION OF AN ADVANCED CELLULAR MODEL TO INVESTIGATE A NOVEL THERAPEUTIC APPROACH FOR SBMA
… is present, the protein presents an elongated polyQ tract (ARpolyQ). When the ARpolyQ protein interacts with DHT, only partial translocation into the nucleus occurs leading to a transcriptional loss of function (LoF), while this interaction also unmasks the polyQ tract, leading to AR toxic gain …
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Role of The Gcn5 Histone Acetyltransferase In Spinocerebellar Ataxia Type 7 and In Immature Neurons
… conflicting evidence regarding the effects of polyQ-ATXN7 on the activity of Gcn5, the HAT catalytic subunit of SAGA. Here I showed that reducing Gcn5 expression accelerates both cerebellar and retinal degeneration in a mouse model of SCA7. Deletion of Gcn5 in Purkinje cells in mice expressing …
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Aneuploidy causes proteotoxic stress in Saccharomyces cerevisiae
… expressed hard to fold proteins such as polyQ stretch-containing proteins. Prion conversion rates are also increased in most aneuploid yeast strains. Protein aggregate formation in aneuploid yeast strains is likely due to limiting protein quality control systems, since I present data …
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Intra-Regional Differences in Cerebellar Vulnerability of Spinocerebellar Ataxia Type 1 Mice
… by an abnormal expansion of polyglutamine (polyQ) repeats in the ATAXIN1 (ATXN1) gene and characterized by cerebellar degeneration. Recent studies in patients with SCA1 indicate that pathogenesis is not uniform across the cerebellum, with posterior vermis and hemispheres exhibiting worse …
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Pharmacological inhibition of CK2: the effect of an FDA designated orphan drug on pathology, neuroinflammation, and glial phenotypes in Huntington’s disease
… and psychological impairments. HD is caused by a polyQ (CAG) repeat expansion in the huntingtin (HTT) gene, leading to the misfolding and aggregation of mutant HTT protein (mHTT) and the preferential degeneration of the striatum. Previously in our lab, we identified Protein Kinase CK2 as an …
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A study on non-canonical autophagy signalling
… such as the neurodegeneration-associated mutant polyQ-huntingtin. This study has identified how ULK1 upregulates autophagy upon glucose starvation and induces the formation of PI(5)P-containing autophagosomes by activating PIKfyve, revealing a novel mechanism by which autophagy is induced.
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The role of Huntingtin in fast axonal transport
… disease that occurs when an expansion of the polyQ tract of the huntingtin gene expands to greater than ~35 residues. This mutation leads to aggregation of the Huntingtin protein (Htt) and degeneration of striatal and cortex neurons, ultimately causing motor impairment and personality changes. …
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Deciphering The Role of Huntingtin In Endosomal Functions
… repeat encoding an extended polyglutamine (polyQ) tract in the coding region of Huntingtin (HTT) gene. While antisense oligonucleotide (ASO) strategies aimed at lowering mutant HTT levels seemed promising, recent clinical trials were unsuccessful due to worsening patient outcomes in the ASO …
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Deciphering The Role of Hsp110 Chaperones In Diseases of Protein Misfolding
… while its overexpression protects against polyQ-mediated neuronal cell death. I hypothesize that in addition to its role as an Hsp70 NEF, <em>Drosophila</em> Hsp110 (Hsc70Cb) may function as a protective protein “holdase”, preventing the aggregation of unfolded polypeptides via the SBD-β …