载脂蛋白E4神经毒作用机制的研究:K~+通道抑制和Ca~(2+)超载
发布时间:2023-04-29 01:51
流行病学调查显示,载脂蛋白E基因(apolipoprotein E gene,APOE)的ε4等位基因是阿尔茨海默病(Alzheimer’s disease,AD)的重要危险因素。研究进一步表明,AD患者脑内的老年斑和神经原纤维缠结中存在有较多的载脂蛋白E4(apolipoprotein E4,apoE4)。该蛋白在脑内由星形胶质细胞以及其它包括神经元在内的多种细胞合成和分泌,其过表达后发挥一定的神经毒性作用。目前,生物化学、细胞生物学、以及转基因动物研究已经提出多种可能的机制来解释apoE4与AD发病的关系,包括:aopE4在淀粉样β蛋白的沉积和清除,以及老年斑形成中的调节作用:削弱机体的抗氧化防御系统:扰乱细胞的信号转导:影响细胞骨架的结构和功能;以及改变tau蛋白的磷酸化状态和形成NFTs等等。多数人还认为,apoE4导致的胞内Ca2+超载可能是上述各种机制的“最后共同通路”。然而,apoE4在脑内引起Ca2+超载和损伤神经元的确切机制尚不清楚,其初始作用以及后续或下游作用如何发生还有待深入研究。 他得注意的是,虽然细胞电活动的...
【文章页数】:124 页
【学位级别】:博士
【文章目录】:
DISSERTATION: The Study on the Neurotoxic Mechanism of Apolipoprotein E4: K+Channel Ca2+-Overloading Suppression and Ca2+
PartⅠ: Effects of Apolipoprotein E4 on Single Channel Delayed-Rectifier K+ Currents in Acutely Isolated Hippocampal Neurons
Abstract
Introduction
Materials and Methods
Results
Discussion
References
PartⅡ: Effects of Apolipoprotein E4 on Whole-cell DelayedRectifierK+CurrentandFast TransientK+CurrentinHippocampal Neurons
Abstract
Introduction
Materials and Methods
Results
Discussion
References
Part Ⅲ: Effects of K+ Currents on [Ca2+]i in Acutely Isolated Hippocampal Neurons
Abstract
Introduction
Materials and Methods
Results
Discussion
References
Part Ⅳ: Apolipoprotein E4 Raised [Ca2+]1 in Acutely Isolated Hippocampal Neurons
Abstract
Introduction
Materials and Methods
Results
Discussion
References
REVIEW: Homocysteine and Alzheimer's disease (in Chinese)
Abstract
Key Word
Text
References
RESUME
ACKNOWLEDGEMENTS (in Chinese)
本文编号:3804917
【文章页数】:124 页
【学位级别】:博士
【文章目录】:
DISSERTATION: The Study on the Neurotoxic Mechanism of Apolipoprotein E4: K+Channel Ca2+-Overloading Suppression and Ca2+
Abstract
Introduction
Materials and Methods
Results
Discussion
References
PartⅡ: Effects of Apolipoprotein E4 on Whole-cell DelayedRectifierK+CurrentandFast TransientK+CurrentinHippocampal Neurons
Abstract
Introduction
Materials and Methods
Results
Discussion
References
Part Ⅲ: Effects of K+ Currents on [Ca2+]i in Acutely Isolated Hippocampal Neurons
Abstract
Introduction
Materials and Methods
Results
Discussion
References
Part Ⅳ: Apolipoprotein E4 Raised [Ca2+]1 in Acutely Isolated Hippocampal Neurons
Abstract
Introduction
Materials and Methods
Results
Discussion
References
REVIEW: Homocysteine and Alzheimer's disease (in Chinese)
Abstract
Key Word
Text
References
RESUME
ACKNOWLEDGEMENTS (in Chinese)
本文编号:3804917
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