摘要
背景:线粒体损伤在阿尔茨海默病(AD)的病理生理学中起着重要作用。然而,在人类进行的研究几乎没有考虑与疾病进展的区域差异。 目的:研究编码线粒体复合物亚基的线粒体复合物亚基和线粒体复合物活性的选择性核基因在内嗅皮层(EC)和额皮质区8(FC)两个区域的表达。 方法:采用qRT-PCR技术从148例病例中分离出冷冻样本,利用商业试剂盒和自制的检测方法测定线粒体复合物I,II,IV和V的活性。 结果:复合体Ⅰ,Ⅱ,Ⅳ和Ⅴ的亚基NDUFA2,NDUFB3,UQCR11,COX7C,ATPD,ATP5L和ATP50的表达下降, II。然而,与EC中的中年个体相比,分离的线粒体的复合物I,II和V的活性在I-II阶段早期发生。相反,在同一系列的FC中没有发现相同基因的表达改变和线粒体复合物活性的改变。 结论:AD可能出现不同的能量代谢受损机制,其中以EC为代表的是线粒体初级和早期改变的结果;另一个可能是功能性输入功能下降的结果,并且在86岁或更小的AD患者中由FC代谢减弱来表示。
关键词: 阿尔茨海默病,线粒体,线粒体磷酸化,代谢减退,基因表达,额叶皮质,内嗅皮层。
Current Alzheimer Research
Title:Reduced Mitochondrial Activity is Early and Steady in the Entorhinal Cortex but it is Mainly Unmodified in the Frontal Cortex in Alzheimer's Disease
Volume: 14 Issue: 12
关键词: 阿尔茨海默病,线粒体,线粒体磷酸化,代谢减退,基因表达,额叶皮质,内嗅皮层。
摘要: Background: It is well established that mitochondrial damage plays a role in the pathophysiology of Alzheimer's disease (AD). However, studies carried out in humans barely contemplate regional differences with disease progression.
Objective: To study the expression of selected nuclear genes encoding subunits of the mitochondrial complexes and the activity of mitochondrial complexes in AD, in two regions: the entorhinal cortex (EC) and frontal cortex area 8 (FC).
Methods: Frozen samples from 148 cases processed for gene expression by qRT-PCR and determination of individual activities of mitochondrial complexes I, II, IV and V using commercial kits and home-made assays.
Results: Decreased expression of NDUFA2, NDUFB3, UQCR11, COX7C, ATPD, ATP5L and ATP50, covering subunits of complex I, II, IV and V, occurs in total homogenates of the EC in AD stages V-VI when compared with stages I-II. However reduced activity of complexes I, II and V of isolated mitochondria occurs as early as stages I-II when compared with middle-aged individuals in the EC. In contrast, no alterations in the expression of the same genes and no alterations in the activity of mitochondrial complexes are found in the FC in the same series.
Conclusion: Different mechanisms of impaired energy metabolism may occur in AD, one of them, represented by the EC, is the result of primary and early alteration of mitochondria; the other one is probably the result, at least in part, of decreased functional input and is represented by hypometabolism in the FC in AD patients aged 86 or younger.
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Reduced Mitochondrial Activity is Early and Steady in the Entorhinal Cortex but it is Mainly Unmodified in the Frontal Cortex in Alzheimer's Disease, Current Alzheimer Research 2017; 14 (12) . https://dx.doi.org/10.2174/1567205014666170505095921
DOI https://dx.doi.org/10.2174/1567205014666170505095921 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
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