Regulation of Alzheimer's disease-associated proteins during epileptogenesis
Regulation of Alzheimer's disease-associated proteins during epileptogenesis
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癫痫发生过程中阿尔茨海默病相关蛋白的调节
DOI：
10.1016/j.neuroscience.2019.08.037
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发表时间：
2020
期刊：
影响因子：
3.3
通讯作者：
Potschka H
中科院分区：
文献类型：
--
作者：
von Rüden EL;Zellinger C;Gedon J;Walker A;Bierling V;Deeg CA;Hauck SM;Potschka H
临床证据和病理学研究表明，颞叶癫痫和阿尔茨海默病(AD)之间存在双向联系。来自组学研究的数据分析提供了一个很好的机会来确定两种病理之间的分子变化重叠。我们对癫痫发生的大鼠模型的蛋白质组数据集进行了生物信息学分析，重点是与AD功能相关的蛋白质。我们的研究证实了与阿尔茨海默病相关的蛋白质调节失调。当比较这两个脑区时，与癫痫发作过程相比，在海马区和海马旁皮质样品中明显存在更显著的调节。失调的蛋白质组包括那些影响线粒体功能和钙稳态的蛋白质组。差异表达的线粒体蛋白包括线粒体复合体I、III、IV和V以及复合体I的附属亚单位的蛋白。分析还发现，潜伏期海马区旁皮质组织中微管相关蛋白Tau的表达存在调节。免疫组织化学进一步证实了这一点。此外，我们还展示了与癫痫发生相关的与淀粉样蛋白β加工及其调控相关的蛋白质的异常调节。其中包括淀粉样前体蛋白和α-分泌酶α去整合素金属蛋白17。我们的分析揭示了与AD发病相关的关键蛋白的相关调节。该分析提供了表征癫痫发展和表现以及AD发展和进展的共同分子变化的全面概述。
Clinical evidence and pathological studies suggest a bidirectional link between temporal lobe epilepsy and Alzheimer’s disease (AD). Data analysis from omic studies offers an excellent opportunity to identify the overlap in molecular alterations between the two pathologies.We have subjected proteomic data sets from a rat model of epileptogenesis to a bioinformatics analysis focused on proteins functionally linked with AD. The data sets have been obtained for hippocampus (HC) and parahippocampal cortex samples collected during the course of epileptogenesis.Our study confirmed a relevant dysregulation of proteins linked with Alzheimer pathogenesis.When comparing the two brain areas, a more prominent regulation was evident in parahippocampal cortex samples as compared to the HC. Dysregulated protein groups comprised those affecting mitochondrial function and calcium homeostasis. Differentially expressed mitochondrial proteins included proteins of the mitochondrial complexes I, III, IV, and V as well as of the accessory subunit of complex I.The analysis also revealed a regulation of the microtubule associated protein Tau in parahippocampal cortex tissue during the latency phase. This was further confirmed by immunohistochemistry.Moreover, we demonstrated a complex epileptogenesis-associated dysregulation of proteins involved in amyloid β processing and its regulation. Among others, the amyloid precursor protein and the α-secretase alpha disintegrin metalloproteinase 17 were included.Our analysis revealed a relevant regulation of key proteins known to be associated with AD pathogenesis. The analysis provides a comprehensive overview of shared molecular alterations characterizing epilepsy development and manifestation as well as AD development and progression.
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影响因子：
6.1
作者：
Keck, Michael;Fournier, Anna;Potschka, Heidrun
通讯作者：
Potschka, Heidrun
DOI：
10.1073/pnas.90.20.9649
发表时间：
1993-10-15
影响因子：
11.1
作者：
SCHMECHEL, DE;SAUNDERS, AM;ROSES, AD
通讯作者：
ROSES, AD
影响因子：
4.1
作者：
Tokuda, T;Calero, M;Ghiso, J
通讯作者：
Ghiso, J
DOI：
10.1016/0013-4694(72)90177-0
发表时间：
1972-01-01
期刊：
ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY
影响因子：
--
作者：
RACINE, RJ
通讯作者：
RACINE, RJ
影响因子：
3
作者：
Hu, Rong;Luo, Jin;Xi, Zhiqin
通讯作者：
Xi, Zhiqin