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淀粉样蛋白和 tau 蛋白特征的共享基因组和蛋白质组学贡献阿尔茨海默病对脑缺血。

Shared Genomic and Proteomic Contribution of Amyloid and Tau Protein Characteristic of Alzheimer's Disease to Brain Ischemia.

机构信息

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.

出版信息

Int J Mol Sci. 2020 Apr 30;21(9):3186. doi: 10.3390/ijms21093186.

Abstract

Post-ischemic brain damage is associated with the deposition of folding proteins such as the amyloid and tau protein in the intra- and extracellular spaces of brain tissue. In this review, we summarize the protein changes associated with Alzheimer's disease and their gene expression (amyloid protein precursor and tau protein) after ischemia-reperfusion brain injury and their role in the post-ischemic injury. Recent advances in understanding the post-ischemic neuropathology have revealed dysregulation of and genes after ischemic brain injury. However, reduced expression of the α-secretase in post-ischemic brain causes neurons to be less resistant to injury. In this review, we present the latest evidence that proteins associated with Alzheimer's disease and their genes play a key role in progressive brain damage due to ischemia and reperfusion, and that an ischemic episode is an essential and leading supplier of proteins and genes associated with Alzheimer's disease in post-ischemic brain. Understanding the underlying processes of linking Alzheimer's disease-related proteins and their genes in post-ischemic brain injury with the risk of developing Alzheimer's disease will provide the most significant goals for therapeutic development to date.

摘要

缺血性脑损伤与折叠蛋白(如淀粉样蛋白和tau 蛋白)在脑组织的细胞内外空间中的沉积有关。在这篇综述中,我们总结了与阿尔茨海默病相关的蛋白变化及其在缺血再灌注脑损伤后的基因表达(淀粉样蛋白前体和 tau 蛋白),以及它们在缺血后损伤中的作用。对缺血后神经病理学的最新认识揭示了缺血性脑损伤后 和 基因的失调。然而,缺血性脑损伤后 α-分泌酶表达减少导致神经元对损伤的抵抗力降低。在这篇综述中,我们提出了最新证据,即与阿尔茨海默病相关的蛋白及其基因在缺血和再灌注引起的进行性脑损伤中起关键作用,而且缺血发作是与缺血性脑内阿尔茨海默病相关的蛋白和基因的重要和主要供应源。了解与缺血后脑损伤中阿尔茨海默病相关蛋白及其基因相关的潜在过程以及发生阿尔茨海默病的风险,将为迄今为止的治疗开发提供最重要的目标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d895/7246538/70e1d09af63b/ijms-21-03186-g001.jpg

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