Laboratory of Ischemic and Neurodegenerative Brain Research, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
First Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland.
J Alzheimers Dis. 2018;66(2):429-437. doi: 10.3233/JAD-180772.
Brain ischemia comprises blood-brain barrier, glial, and neuronal cells. The blood-brain barrier controls permeability of different substances and the composition of the neuronal cells 'milieu', which is required for their physiological functioning. Recent evidence indicates that brain ischemia itself and ischemic blood-brain barrier dysfunction is associated with the accumulation of neurotoxic molecules within brain tissue, e.g., different parts of amyloid-β protein precursor and changed pathologically tau protein. All these changes due to ischemia can initiate and progress neurodegeneration of the Alzheimer's disease-type. This review presents brain ischemia and ischemic blood-brain barrier as a trigger for tau protein alterations. Thus, we hypothesize that the changes in pattern of phosphorylation of tau protein are critical to microtubule function especially in neurons, and contribute to the neurodegeneration following brain ischemia-reperfusion episodes with Alzheimer's disease phenotype.
脑缺血包括血脑屏障、神经胶质细胞和神经元细胞。血脑屏障控制着不同物质的通透性和神经元细胞环境的组成,这是它们生理功能所必需的。最近的证据表明,脑缺血本身和缺血性血脑屏障功能障碍与脑内神经毒性分子的积累有关,例如,淀粉样β蛋白前体的不同部分和病理性改变的 tau 蛋白。所有这些由于缺血引起的变化都可能引发阿尔茨海默病型的神经退行性变。这篇综述介绍了脑缺血和缺血性血脑屏障作为 tau 蛋白改变的触发因素。因此,我们假设 tau 蛋白磷酸化模式的变化对微管功能至关重要,特别是在神经元中,并有助于阿尔茨海默病表型的脑缺血再灌注后神经退行性变。