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 Jun 28;21(13):4599. doi: 10.3390/ijms21134599.
Current evidence indicates that postischemic brain injury is associated with the accumulation of folding proteins, such as amyloid and tau protein, in the intra- and extracellular spaces of neuronal cells. In this review, we summarize protein changes associated with Alzheimer's disease and their gene expression (amyloid protein precursor and tau protein) after brain ischemia, and their roles in the postischemic period. Recent advances in understanding the postischemic mechanisms in development of neurodegeneration have revealed dysregulation of amyloid protein precursor, α-, β- and γ-secretase and tau protein genes. Reduced expression of the α-secretase gene after brain ischemia with recirculation causes neuronal cells to be less resistant to injury. We present the latest data that Alzheimer's disease-related proteins and their genes play a crucial role in postischemic neurodegeneration. Understanding the underlying processes of linking Alzheimer's disease-related proteins and their genes in development of postischemic neurodegeneration will provide the most significant goals to date for therapeutic development.
目前的证据表明，缺血性脑损伤与神经元细胞内和细胞外空间中折叠蛋白（如淀粉样蛋白和tau 蛋白）的积累有关。在这篇综述中，我们总结了与阿尔茨海默病相关的蛋白质变化及其脑缺血后基因表达（淀粉样蛋白前体和 tau 蛋白），并探讨了它们在缺血后时期的作用。近年来，对缺血后神经退行性变发展中机制的理解揭示了淀粉样蛋白前体、α-、β-和 γ-分泌酶和 tau 蛋白基因的失调。脑缺血再灌注后 α-分泌酶基因表达减少导致神经元细胞对损伤的抵抗力降低。我们呈现了最新的数据，表明与阿尔茨海默病相关的蛋白质及其基因在缺血性神经退行性变中起着至关重要的作用。了解与阿尔茨海默病相关的蛋白质及其基因在缺血性神经退行性变发展中的联系的潜在过程，将为治疗开发提供迄今为止最重要的目标。
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