Department of Pathophysiology, Medical University of Lublin, 20-090 Lublin, Poland.
Int J Mol Sci. 2024 Mar 7;25(6):3091. doi: 10.3390/ijms25063091.
Recent evidence indicates that experimental brain ischemia leads to dementia with an Alzheimer's disease-like type phenotype and genotype. Based on the above evidence, it was hypothesized that brain ischemia may contribute to the development of Alzheimer's disease. Brain ischemia and Alzheimer's disease are two diseases characterized by similar changes in the hippocampus that are closely related to memory impairment. Following brain ischemia in animals and humans, the presence of amyloid plaques in the extracellular space and intracellular neurofibrillary tangles was revealed. The phenomenon of tau protein hyperphosphorylation is a similar pathological feature of both post-ischemic brain injury and Alzheimer's disease. In Alzheimer's disease, the phosphorylated Thr231 motif in tau protein has two distinct and conformations and is the primary site of tau protein phosphorylation in the pre-entanglement cascade and acts as an early precursor of tau protein neuropathology in the form of neurofibrillary tangles. Based on the latest publication, we present a similar mechanism of the formation of neurofibrillary tangles after brain ischemia as in Alzheimer's disease, established on - and -phosphorylation of tau protein, which ultimately influences the development of tauopathy.
近期证据表明,实验性脑缺血可导致具有阿尔茨海默病样表型和基因型的痴呆。基于上述证据,有人假设脑缺血可能导致阿尔茨海默病的发生。脑缺血和阿尔茨海默病是两种以海马区相似变化为特征的疾病,与记忆障碍密切相关。在动物和人类发生脑缺血后,细胞外空间和细胞内神经原纤维缠结中出现淀粉样斑块。tau 蛋白过度磷酸化的现象是缺血后脑损伤和阿尔茨海默病的相似病理特征。在阿尔茨海默病中,tau 蛋白中 Thr231 位的磷酸化 Thr231 模体具有两种独特的构象,是 tau 蛋白预缠结级联中 tau 蛋白磷酸化的主要位点,并以神经原纤维缠结的形式作为 tau 蛋白神经病理学的早期前体。基于最新的出版物,我们提出了脑缺血后形成神经原纤维缠结的类似机制,该机制建立在 tau 蛋白的 -和 -磷酸化上,最终影响了 tau 病的发展。