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首页> 外文期刊>Journal of Molecular Biology >Ursodeoxycholic Acid Improves Mitochondrial Function and Redistributes Drp1 in Fibroblasts from Patients with Either Sporadic or Familial Alzheimer's Disease
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Ursodeoxycholic Acid Improves Mitochondrial Function and Redistributes Drp1 in Fibroblasts from Patients with Either Sporadic or Familial Alzheimer's Disease

机译：核糖核酸改善线粒体功能，并重新分配来自孢子或家族性阿尔茨海默病患者的成纤维细胞中的DRP1

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Alzheimer's disease (AD) is the leading cause of dementia worldwide. Mitochondrial abnormalities have been identified in many cell types in AD, with deficits preceding the development of the classical pathological aggregations. Ursodeoxycholic acid (UDCA), a treatment for primary biliary cirrhosis, improves mitochondrial function in fibroblasts derived from Parkinson's disease patients as well as several animal models of AD and Parkinson's disease. In this paper, we investigated both mitochondrial function and morphology in fibroblasts from patients with both sporadic and familial AD. We show that both sporadic AD (sAD) and PSEN1 fibroblasts share the same impairment of mitochondrial membrane potential and alterations in mitochondrial morphology. Mitochondrial respiration, however, was decreased in sAD fibroblasts and increased in PSEN1 fibroblasts. Morphological changes seen in AD fibroblasts include reduced mitochondrial number and increased mitochondrial clustering around the cell nucleus as well as an increased number of long mitochondria. We show here for the first time in AD patient tissue that treatment with UDCA increases mitochondrial membrane potential and respiration as well as reducing the amount of long mitochondria in AD fibroblasts. In addition, we show reductions in dynamin-related protein 1 (Drp1) level, particularly the amount localized to mitochondria in both sAD and familial patient fibroblasts. Drp1 protein amount and localization were increased after UDCA treatment. The restorative effects of UDCA are abolished when Drp1 is knocked down. This paper highlights the potential use of UDCA as a treatment for neurodegenerative disease.
机译：阿尔茨海默病（AD）是全球痴呆症的主要原因。在广告中的许多细胞类型中已经鉴定了线粒体异常，并且在经典病理聚集的发展之前的缺陷。熊去氧胆酸（UDCA），对于原发性胆汁性肝硬化治疗，改善帕金森病的患者以及AD的几种动物模型和帕金森氏病的成纤维细胞的线粒体功能。在本文中，我们研究了来自零星和家族广告患者的成纤维细胞的线粒体功能和形态。我们表明，两种零星AD（SAD）和PSEN1成纤维细胞均有相同的线粒体膜潜力和线粒体形态的改变。然而，线粒体呼吸在悲伤的成纤维细胞中降低，并且在psen1成纤维细胞中增加。 AD成纤维细胞中可见的形态学变化包括减少的线粒体数，并在细胞核周围增加线粒体聚类，以及长线粒体数量增加。我们在这里首次在AD患者组织中展示，用UDCA治疗增加线粒体膜电位和呼吸，以及减少广告成纤维细胞的长线粒体量。此外，我们展示了Dynamin相关蛋白1（DRP1）水平的降低，特别是悲伤和家族性患者成纤维细胞中局限于线粒体的量。 UDCA治疗后DRP1蛋白质量和定位增加。当DRP1被击倒时，UDCA的修复效果被废除。本文突出了UDCA作为神经变性疾病治疗的潜在用途。

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