摘要
视黄酸、β-胡萝卜素的生物活性代谢物或维生素A,在脊椎动物发展发挥了多效性的、多功能的作用。在啮齿动物的研究显示,饮食中缺乏维生素a的结果会导致一个复杂的新生儿综合症(VAD综合症),并且体现在许多器官中。在人类中,维甲酸(RA)的功能延伸到成年,对生育,视觉,抑制肿瘤的生长有重要作用。近年来,它也表明,维甲酸可能作为衰减治疗甚至预防神经退行性疾病如阿尔茨海默病(AD) 的相关药物。在这里,我们报告和监督增加a -β-淀粉样蛋白肽水平只有轻微的影响,表达水平的观察淀粉样前体蛋白(APP)加工蛋白酶在野生型老鼠的实验中。符合这些发现, 减少维生素缺乏的救援a -β-淀粉样蛋白量到基线和诱导sApp-alpha分泌结合增加alpha-secretase Adam10。通过比较从一个完整的营养状态和人类神经母细胞瘤细胞的维甲酸治疗 “监督”的局势,我们表明,在基因差异表达的强度高于补充细胞,观察AD-related与调节基因大幅重叠。我们的数据表明,维生素缺乏会引起阿尔茨海默病的发作或恶化,通过增加A -β-淀粉样蛋白肽的合成,几个AD-related如ADAM10或BDNF基因是由视黄酸组成的。我们建议膳食视黄酸衍生品补充剂可能有益影响AD-pathology患者在患有维生素缺乏中保持维生素状态正常。
关键词: 阿尔茨海默病、A -β-淀粉样蛋白肽、alpha-secretase核受体、视黄酸、脱落、维生素A。
Current Alzheimer Research
Title:Rescue of Hypovitaminosis A Induces Non-Amyloidogenic Amyloid Precursor Protein (APP) Processing
Volume: 13 Issue: 11
Author(s): Sven Reinhardt, Marcus O.W. Grimm, Christoph Stahlmann, Tobias Hartmann, Koichi Shudo, Taisuke Tomita, Kristina Endres
Affiliation:
关键词: 阿尔茨海默病、A -β-淀粉样蛋白肽、alpha-secretase核受体、视黄酸、脱落、维生素A。
摘要: Retinoic acid, the bioactive metabolite of beta-carotene or vitamin A, plays a pleiotropic, multifunctional role in vertebrate development. Studies in rodents revealed that a diet deficient in vitamin A results in a complex neonatal syndrome (the VAD syndrome), manifested in many organs. In humans, the function of retinoic acid (RA) extends into adulthood, where it has important roles in fertility, vision, and suppression of neoplastic growth. In recent years, it has also been suggested that retinoic acid might potentially act as a therapeutically relevant drug in attenuating or even preventing neurodegenerative diseases such as Alzheimer’s disease (AD). Here, we report that VAD leads to an increase in A-beta peptide levels while only minor effects were observed on expression levels of the amyloid precursor protein (APP) processing proteinases in wild type mice. In line with these findings, rescue of hypovitaminosis reduced A-beta amount to baseline and induced sApp-alpha secretion in combination with an increase of alpha-secretase Adam10. By comparing retinoic acid treatment starting from a full nutrition status and a “VAD” situation in human neuroblastoma cells, we show that while intensities of differential gene expression were higher in replenished cells, a large overlap in AD-related, regulated genes was observed. Our data suggest that hypovitaminosis A can contribute to onset or progression of AD by increasing synthesis of A-beta peptides and that several AD-related genes such as ADAM10 or BDNF are regulated by retinoic acid. We suggest that dietary supplementation with retinoic acid derivatives is likely to have a beneficial effect on AD-pathology in individuals with hypovitaminosis and patients with normal vitamin A status.
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Sven Reinhardt, Marcus O.W. Grimm, Christoph Stahlmann, Tobias Hartmann, Koichi Shudo, Taisuke Tomita, Kristina Endres , Rescue of Hypovitaminosis A Induces Non-Amyloidogenic Amyloid Precursor Protein (APP) Processing, Current Alzheimer Research 2016; 13 (11) . https://dx.doi.org/10.2174/1567205013666160603002105
DOI https://dx.doi.org/10.2174/1567205013666160603002105 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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