Laboratory of Ischemic and Neurodegenerative Brain Research, Mossakowski Medical Research Centre, Polish Academy of Sciences, 02-106 Warsaw, Poland.
Department of Pathophysiology, Medical University of Lublin, 20-090 Lublin, Poland.
Int J Mol Sci. 2020 Jan 30;21(3):892. doi: 10.3390/ijms21030892.
Recent evidence suggests that transient ischemia of the brain with reperfusion in humans and animals is associated with the neuronal accumulation of neurotoxic molecules associated with Alzheimer's disease, such as all parts of the amyloid protein precursor and modified tau protein. Pathological changes in the amyloid protein precursor and tau protein at the protein and gene level due to ischemia may lead to dementia of the Alzheimer's disease type after ischemic brain injury. Some studies have demonstrated increased tau protein immunoreactivity in neuronal cells after brain ischemia-reperfusion injury. Recent research has presented many new tau protein functions, such as neural activity control, iron export, protection of genomic DNA integrity, neurogenesis and long-term depression. This review discusses the potential mechanisms of tau protein in the brain after ischemia, including oxidative stress, apoptosis, autophagy, excitotoxicity, neurological inflammation, endothelium, angiogenesis and mitochondrial dysfunction. In addition, attention was paid to the role of tau protein in damage to the neurovascular unit. Tau protein may be at the intersection of many regulatory mechanisms in the event of major neuropathological changes in ischemic stroke. Data show that brain ischemia activates neuronal changes and death in the hippocampus in a manner dependent on tau protein, thus determining a new and important way to regulate the survival and/or death of post-ischemic neurons. Meanwhile, the association between tau protein and ischemic stroke has not been well discussed. In this review, we aim to update the knowledge about the proteomic and genomic changes in tau protein following ischemia-reperfusion injury and the connection between dysfunctional tau protein and ischemic stroke pathology. Finally we present the positive correlation between tau protein dysfunction and the development of sporadic Alzheimer's disease type of neurodegeneration.
最近的证据表明，人类和动物的短暂脑缺血再灌注与阿尔茨海默病相关的神经毒性分子的神经元积累有关，如淀粉样蛋白前体的所有部分和修饰的tau 蛋白。缺血引起的淀粉样蛋白前体和 tau 蛋白在蛋白质和基因水平上的病理变化可能导致缺血性脑损伤后的阿尔茨海默病型痴呆。一些研究表明，脑缺血再灌注损伤后神经元细胞中的 tau 蛋白免疫反应性增加。最近的研究提出了 tau 蛋白的许多新功能，如神经活动控制、铁输出、保护基因组 DNA 完整性、神经发生和长时程抑制。本文讨论了 tau 蛋白在脑缺血后的潜在机制，包括氧化应激、细胞凋亡、自噬、兴奋毒性、神经炎症、内皮细胞、血管生成和线粒体功能障碍。此外，还关注了 tau 蛋白在神经血管单元损伤中的作用。在缺血性中风等重大神经病理学变化的情况下，tau 蛋白可能处于许多调节机制的交汇点。有数据表明，脑缺血以依赖于 tau 蛋白的方式激活海马中的神经元变化和死亡，从而确定了一种调节缺血后神经元存活和/或死亡的新的重要方式。同时，tau 蛋白与缺血性中风之间的关联尚未得到很好的讨论。在本文中，我们旨在更新关于缺血再灌注损伤后 tau 蛋白的蛋白质组学和基因组学变化以及功能失调的 tau 蛋白与缺血性中风病理学之间联系的知识。最后，我们提出 tau 蛋白功能障碍与散发性阿尔茨海默病型神经退行性变的发展之间存在正相关。
