Slower Dynamics and Aged Mitochondria in Sporadic Alzheimer's Disease.
Slower Dynamics and Aged Mitochondria in Sporadic Alzheimer's Disease.
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DOI：
10.1155/2017/9302761
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发表时间：
2017
影响因子：
--
通讯作者：
García-Escudero V
中科院分区：
文献类型：
--
作者：
Martín-Maestro P;Gargini R;García E;Perry G;Avila J;García-Escudero V
散发性阿尔茨海默病相当于95%的病例，其起源是多因素的和难以捉摸的。线粒体功能障碍是阿尔茨海默病的主要病理特征，可能是触发下游主要事件的早期事件之一。在这里，我们展示了控制线粒体动态平衡的多个基因，包括分裂和融合，在阿尔茨海默氏症患者中下调。此外，我们证明了其中一些失调，如DLP1水平降低及其线粒体定位，以及STOML2和Mfn2融合蛋白水平降低，发生在散发性阿尔茨海默病患者的成纤维细胞中。CCCP对线粒体网络破坏的分析表明，患者的成纤维细胞动力学和线粒体膜电位恢复较慢。这些缺陷导致阿尔茨海默氏症成纤维细胞中老化的线粒体大量积累。因此，对患者中涉及自噬和有丝分裂吞噬的基因的分析表明，这些老化的线粒体的循环机制可能受到了下调。我们的数据强化了线粒体功能障碍是与衰老密切相关的疾病早期关键事件之一的观点。
Sporadic Alzheimer's disease corresponds to 95% of cases whose origin is multifactorial and elusive. Mitochondrial dysfunction is a major feature of Alzheimer's pathology, which might be one of the early events that trigger downstream principal events. Here, we show that multiple genes that control mitochondrial homeostasis, including fission and fusion, are downregulated in Alzheimer's patients. Additionally, we demonstrate that some of these dysregulations, such as diminished DLP1 levels and its mitochondrial localization, as well as reduced STOML2 and MFN2 fusion protein levels, take place in fibroblasts from sporadic Alzheimer's disease patients. The analysis of mitochondrial network disruption using CCCP indicates that the patients' fibroblasts exhibit slower dynamics and mitochondrial membrane potential recovery. These defects lead to strong accumulation of aged mitochondria in Alzheimer's fibroblasts. Accordingly, the analysis of autophagy and mitophagy involved genes in the patients demonstrates a downregulation indicating that the recycling mechanism of these aged mitochondria might be impaired. Our data reinforce the idea that mitochondrial dysfunction is one of the key early events of the disease intimately related with aging.
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影响因子：
17.7
作者：
Alexander, GE;Chen, K;Reiman, EM
通讯作者：
Reiman, EM
DOI：
10.1111/j.1749-6632.2000.tb06370.x
发表时间：
2000-01-01
期刊：
VASCULAR FACTORS IN ALZHEIMER'S DISEASE
影响因子：
--
作者：
Blass, JP;Sheu, RKF;Gibson, GE
通讯作者：
Gibson, GE
DOI：
10.3233/jad-2010-100552
发表时间：
2010
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Bossy B;Petrilli A;Klinglmayr E;Chen J;Lütz-Meindl U;Knott AB;Masliah E;Schwarzenbacher R;Bossy-Wetzel E
通讯作者：
Bossy-Wetzel E
影响因子：
1.7
作者：
Mattson, MP;Fu, WM;Uchida, K
通讯作者：
Uchida, K
影响因子：
3.5
作者：
Martin-Maestro, Patricia;Gargini, Ricardo;Garcia-Escudero, Vega
通讯作者：
Garcia-Escudero, Vega