Increased Active OMI/HTRA2 Serine Protease Displays a Positive Correlation with Cholinergic Alterations in the Alzheimer's Disease Brain.
Increased Active OMI/HTRA2 Serine Protease Displays a Positive Correlation with Cholinergic Alterations in the Alzheimer's Disease Brain.
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DOI：
10.1007/s12035-018-1383-3
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发表时间：
2019-07
影响因子：
5.1
通讯作者：
Behbahani H
中科院分区：
文献类型：
--
作者：
Darreh-Shori T;Rezaeianyazdi S;Lana E;Mitra S;Gellerbring A;Karami A;Bogdanovic N;Lithner CU;Winblad B;Behbahani H
OMI/HTRA 2（高温需要丝氨酸蛋白酶A2）是一种线粒体丝氨酸蛋白酶，参与多种细胞过程，包括自噬，伴侣活性和凋亡。关于OMI/HTRA 2在阿尔茨海默病（Alzheimer's disease，AD）中的作用的研究很少，但关于OMI/HTRA 2与胆碱能系统、神经营养因子以及其他AD相关蛋白的关系的研究还未见报道。在这项研究中，免疫组织化学分析显示，AD患者有更高的OMI/HTRA 2蛋白质的胞质分布相比，对照组。对脑提取物的定量分析表明AD脑中OMI/HTRA 2的活性形式显著增加。激活的OMI/HTRA 2蛋白与应激相关的通读乙酰胆碱酯酶活性呈正相关。此外，α7烟碱乙酰胆碱受体基因表达，一种已知也位于线粒体外膜上的受体，在三个不同的脑区域中与OMI/HTRA 2基因表达表现出强相关性。有趣的是，激活的OMI/HTRA 2水平也与乙酰胆碱生物合成酶，胆碱乙酰转移酶（ChAT）的活性相关;与神经营养因子，NGF和BDNF的水平相关;与淀粉样蛋白前体蛋白（APP）的可溶性片段的水平相关;以及与微管相关蛋白tau的基因表达相关。总体而言，结果表明线粒体丝氨酸蛋白酶OMI/HTRA 2的水平增加，以及OMI/HTRA 2的活化形式与AD病理学中涉及的几种关键蛋白质之间的相关模式。在本文中，我们提出了一个新的假设模型，强调OMI/HTRA 2在线粒体功能和AD中的作用的重要性和需要进一步调查。本文的在线版本（10.1007/s12035-018-1383-3）包含补充材料，可供授权用户使用。
OMI/HTRA2 (high-temperature requirement serine protease A2) is a mitochondrial serine protease involved in several cellular processes, including autophagy, chaperone activity, and apoptosis. Few studies on the role of OMI/HTRA2 in Alzheimer’s disease (AD) are available, but none on its relationship with the cholinergic system and neurotrophic factors as well as other AD-related proteins. In this study, immunohistochemical analyses revealed that AD patients had a higher cytosolic distribution of OMI/HTRA2 protein compared to controls. Quantitative analyses on brain extracts indicated a significant increase in the active form of OMI/HTRA2 in the AD brain. Activated OMI/HTRA2 protein positively correlated with stress-associated read-through acetylcholinesterase activity. In addition, α7 nicotinic acetylcholine receptor gene expression, a receptor also known to be localized on the outer membrane of mitochondria, showed a strong correlation with OMI/HTRA2 gene expression in three different brain regions. Interestingly, the activated OMI/HTRA2 levels also correlated with the activity of the acetylcholine-biosynthesizing enzyme, choline acetyltransferase (ChAT); with levels of the neurotrophic factors, NGF and BDNF; with levels of the soluble fragments of amyloid precursor protein (APP); and with gene expression of the microtubule-associated protein tau in the examined brain regions. Overall, the results demonstrate increased levels of the mitochondrial serine protease OMI/HTRA2, and a coherent pattern of association between the activated form of OMI/HTRA2 and several key proteins involved in AD pathology. In this paper, we propose a new hypothetical model to highlight the importance and needs of further investigation on the role of OMI/HTRA2 in the mitochondrial function and AD. The online version of this article (10.1007/s12035-018-1383-3) contains supplementary material, which is available to authorized users.
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影响因子：
4.2
作者：
Darreh-Shori, Taher;Vijayaraghavan, Swetha;Nordberg, Agneta
通讯作者：
Nordberg, Agneta
DOI：
10.1016/j.biocel.2014.01.001
发表时间：
2014-04-01
影响因子：
4
作者：
Gergalova, Galyna;Lykhmus, Olena;Skok, Maryna
通讯作者：
Skok, Maryna
DOI：
10.1073/pnas.0135647100
发表时间：
2003-01-07
影响因子：
11.1
作者：
Birikh, KR;Sklan, EH;Soreq, H
通讯作者：
Soreq, H
影响因子：
5.6
作者：
Chernyavsky, Alex I.;Shchepotin, Igor B.;Grando, Sergei A.
通讯作者：
Grando, Sergei A.
影响因子：
6.1
作者：
Albers, Shawn;Inthathirath, Fatima;Rylett, R. Jane
通讯作者：
Rylett, R. Jane