Post-translational modifications of Tau-linked neurodegenerative disorders in a Drosophila model
碩士 === 國立清華大學 === 生物科技研究所 === 101 === Tauopathies are a class of neurodegenerative diseases associated with the pathological aggregation of tau. Tau is a microtubule-associated protein predominantly expressed in nerve cells and its main function is to stabilize the microtubules and to regulate the d...
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ndltd-TW-101NTHU51111502015-10-13T22:29:58Z http://ndltd.ncl.edu.tw/handle/82520842572969267233 Post-translational modifications of Tau-linked neurodegenerative disorders in a Drosophila model 在果蠅模式中探討 Tau 蛋白經轉譯後修飾與 其所引發的神經毒性之關係 Shiu, Ren-Huei 徐仁慧 碩士 國立清華大學 生物科技研究所 101 Tauopathies are a class of neurodegenerative diseases associated with the pathological aggregation of tau. Tau is a microtubule-associated protein predominantly expressed in nerve cells and its main function is to stabilize the microtubules and to regulate the dynamic of tubulin assembly. Accumulated studies have demonstrated that Tau hyperphosphorylation, nonphosphorylation and truncation play important roles for Tau-induced cytotoxicity. However, the question of whether Tau truncation or phosphorylation linking to the underlying pathogenic mechanism of tauopathies is under debates. To investigate which event is more critical for Tau-induced pathology, we generated transgenic flies with modified phosphorylation and truncation sites, and employed fly eye as a model to elucidate the effect of post-translational modification in tau-mediated toxicity in vivo. We found that hTau-E14FL and hTau-APFL have eye phenotype and further speculate that both hyperphosphorylated and nonphosphorylated full length hTau have detrimental effect. Interestingly, our data indicate that expressing truncated and psudophosphorylated hTau without the least twenty amino acids (hTau-E14421) only showed mild eye degeneration. Hence, we suggest that posttranslational modification of Tau C-terminus may be critical for Tau-induced pathology. Since the aforementioned C-terminal fragment contains a putative casein kinase site and a glycosylation site, we further manipulated casein kinase activity and glycosylated enzyme activity to validate the significance of the potential modifications. Based on the genetic data, we suggest that casein kinase may play a crucial role for tau-mediated neurotoxicity. This study may provide a mechanistic insight for developing the therapeutic targets for mitigating pathogenic tau-related neurodegeneration. Sang, Tzu-Kang 桑自剛 2013 學位論文 ; thesis 61 zh-TW |
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碩士 === 國立清華大學 === 生物科技研究所 === 101 === Tauopathies are a class of neurodegenerative diseases associated with the pathological aggregation of tau. Tau is a microtubule-associated protein predominantly expressed in nerve cells and its main function is to stabilize the microtubules and to regulate the dynamic of tubulin assembly. Accumulated studies have demonstrated that Tau hyperphosphorylation, nonphosphorylation and truncation play important roles for Tau-induced cytotoxicity. However, the question of whether Tau truncation or phosphorylation linking to the underlying pathogenic mechanism of tauopathies is under debates. To investigate which event is more critical for Tau-induced pathology, we generated transgenic flies with modified phosphorylation and truncation sites, and employed fly eye as a model to elucidate the effect of post-translational modification in tau-mediated toxicity in vivo. We found that hTau-E14FL and hTau-APFL have eye phenotype and further speculate that both hyperphosphorylated and nonphosphorylated full length hTau have detrimental effect. Interestingly, our data indicate that expressing truncated and psudophosphorylated hTau without the least twenty amino acids (hTau-E14421) only showed mild eye degeneration. Hence, we suggest that posttranslational modification of Tau C-terminus may be critical for Tau-induced pathology. Since the aforementioned C-terminal fragment contains a putative casein kinase site and a glycosylation site, we further manipulated casein kinase activity and glycosylated enzyme activity to validate the significance of the potential modifications. Based on the genetic data, we suggest that casein kinase may play a crucial role for tau-mediated neurotoxicity. This study may provide a mechanistic insight for developing the therapeutic targets for mitigating pathogenic tau-related neurodegeneration.
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Sang, Tzu-Kang |
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Sang, Tzu-Kang Shiu, Ren-Huei 徐仁慧 |
author |
Shiu, Ren-Huei 徐仁慧 |
spellingShingle |
Shiu, Ren-Huei 徐仁慧 Post-translational modifications of Tau-linked neurodegenerative disorders in a Drosophila model |
author_sort |
Shiu, Ren-Huei |
title |
Post-translational modifications of Tau-linked neurodegenerative disorders in a Drosophila model |
title_short |
Post-translational modifications of Tau-linked neurodegenerative disorders in a Drosophila model |
title_full |
Post-translational modifications of Tau-linked neurodegenerative disorders in a Drosophila model |
title_fullStr |
Post-translational modifications of Tau-linked neurodegenerative disorders in a Drosophila model |
title_full_unstemmed |
Post-translational modifications of Tau-linked neurodegenerative disorders in a Drosophila model |
title_sort |
post-translational modifications of tau-linked neurodegenerative disorders in a drosophila model |
publishDate |
2013 |
url |
http://ndltd.ncl.edu.tw/handle/82520842572969267233 |
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