臺灣博碩士論文加值系統

Tauopathies are characterized by the intraneuronal inclusions of hyperphosphorylated tau in human brain. Tau is a microtubule-associated protein, which stabilizes the microtubules cytoskeleton and regulates the dynamic of tubulin assembly. Recent studies have demonstrated that mutations in certain sites of Tau that associated with autosomal dominant tauopathy FTDP-17 (frontotemporal dementia with parkinsonism linked to chromosome 17) can lead to hyperphosphorylated tau aggregates in the neurons. While Tau protein phosphorylation is the major focus of tauopathies studies, several reports found that Tau-induced cytotoxicity could be uncoupled with its phosphorylation state. Here, we have employed a well-characterized Drosophila model of tauopathy to investigate whether the toxicity of tau is due to the cleavage by Caspases. Overexpression of human tau in fly recapitulates the features of tauopathies, and the phenotype could be suppressed by RNA interference (RNAi)-mediated knockdown of selected Drosophila Caspases. Surprisingly, we observe that under the condition of the equivalent expression of wild type tau and tau with mutation of a Caspase cleavage site (TauD421A), the eye phenotype is strikingly mild in TauD421A as compared to the Tauwt, suggesting that the processing of tau by caspase is crucial for the tau-mediated cytotoxicity. Our data provide an important insight into tauopathies and help to understand the molecular mechanism of tau-related neurodegeneration.

Introduction……………………………………………………………..1
中文摘要………………..………………………………………………3
Acknowledgement…..…………..………………………………………4

Introduction………………..……………………………….…………...6

Materials and methods………………………………………………....9

Results…………………………………………………………………..14

Discussion……………….……………………………………………...20

Figures….……………….……………………………………………...25

Reference….……………….…………………………………………...48

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